Principles of Development 6th Edition

Lewis Wolpert
Visit to download the full and correct content document:
https://textbookfull.com/product/principles-of-development-6th-edition-lewis-wolpert/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Principles of Information Security 6th Edition Whitman

https://textbookfull.com/product/principles-of-information-
security-6th-edition-whitman/

The Power of Critical Thinking: Effective Reasoning

about Ordinary and Extraordinary Claims (6th Ed.) 6th
Edition Lewis Vaughn

https://textbookfull.com/product/the-power-of-critical-thinking-
effective-reasoning-about-ordinary-and-extraordinary-claims-6th-
ed-6th-edition-lewis-vaughn/

Ideas Of Power The Politics Of American Party Ideology

Development Verlan Lewis

https://textbookfull.com/product/ideas-of-power-the-politics-of-
american-party-ideology-development-verlan-lewis/

Bioethics Principles, Issues, And Cases (3rd Ed.) 3rd

Edition Lewis Vaughn

https://textbookfull.com/product/bioethics-principles-issues-and-
cases-3rd-ed-3rd-edition-lewis-vaughn/
Bioethics : principles, issues, and cases (4th Ed.)
Fourth Edition Lewis Vaughn

https://textbookfull.com/product/bioethics-principles-issues-and-
cases-4th-ed-fourth-edition-lewis-vaughn/

Genetics : analysis & principles 6th Edition Robert J.

Brooker

https://textbookfull.com/product/genetics-analysis-
principles-6th-edition-robert-j-brooker/

Theories of development : concepts and applications 6th

Edition William Crain

https://textbookfull.com/product/theories-of-development-
concepts-and-applications-6th-edition-william-crain/

Nuclear Cardiac Imaging: Principles and Applications

6th Edition Ami E. Iskandrian

https://textbookfull.com/product/nuclear-cardiac-imaging-
principles-and-applications-6th-edition-ami-e-iskandrian/

The Wolff-Kishner Reduction and Related Reactions:

Discovery and Development 1st Edition David E. Lewis

https://textbookfull.com/product/the-wolff-kishner-reduction-and-
related-reactions-discovery-and-development-1st-edition-david-e-
lewis/
Principles of Development
 Principles of Development
Sixth Edition

Lewis Wolpert | Cheryll Tickle | Alfonso Martinez Arias

Peter Lawrence

James Locke

1
 1
Great Clarendon Street, Oxford, OX2 6DP,
United Kingdom
Oxford University Press is a department of the University of Oxford.
It furthers the University’s objective of excellence in research, scholarship,
and education by publishing worldwide. Oxford is a registered trade mark of
Oxford University Press in the UK and in certain other countries

© Oxford University Press 2019

The moral rights of the authors have been asserted
Third edition 2006
Fourth edition 2011
Fifth edition 2015
Impression: 1
All rights reserved. No part of this publication may be reproduced, stored in
a retrieval system, or transmitted, in any form or by any means, without the
prior permission in writing of Oxford University Press, or as expressly permitted
by law, by licence or under terms agreed with the appropriate reprographics
rights organization. Enquiries concerning reproduction outside the scope of the
above should be sent to the Rights Department, Oxford University Press, at the
address above
You must not circulate this work in any other form
and you must impose this same condition on any acquirer
Published in the United States of America by Oxford University Press
198 Madison Avenue, New York, NY 10016, United States of America
British Library Cataloguing in Publication Data
Data available
Library of Congress Control Number: 2018959364
ISBN 978–0–19–252081–4
Printed in Great Britain by
Bell & Bain Ltd., Glasgow
Links to third party websites are provided by Oxford in good faith and
for information only. Oxford disclaims any responsibility for the materials
contained in any third party website referenced in this work.
Preface

The fundamental questions about how an embryo develops into a new individual
were posed long ago by the ancient Greek scientists and philosophers. Over the cen-
turies, advances in experimental embryology and, more recently, the application
of genetics, cell biology, and advances in imaging have revealed many similarities
between the development of different organisms, particularly during the early stages,
suggesting the existence of general principles underlying the process. Developmental
biology is now a mature discipline, and this is the foundation on which this book,
focused on principles, was built. We have not included in this sixth edition every new
detail that has emerged since the previous edition, which are many and wonderful,
but instead, where appropriate, have provided up-to-date examples to illustrate the
general principles.
Principles of Development is designed for undergraduates, and we have tried to
make these principles as clear as possible and to provide numerous summaries, in
both words and pictures. As we understand the principles better, the book should
become shorter, but we have not yet achieved this!
We concentrate on the development of vertebrates and Drosophila but include other
organisms, such as the nematode, the sea urchin, Hydra, planarians, and crustaceans,
where they best illustrate a concept. Chapter 1 provides a brief history of embryology
and an introduction to some of the main general principles and processes involved.
Chapter 2 considers the process of pattern formation in laying down the body plan in
Drosophila (Chapter 2). This small fly has played, and still plays, a central role in elu-
cidating developmental mechanisms. Chapter 3 describes the embryology and genetics
of our vertebrate model organisms—Xenopus, zebrafish, chick, and mouse—together
with some of the main methods used to study them, with coverage in this edition of
new methods of gene editing such as CRISPR-Cas9. Although the fundamental prin-
ciples of development are still largely illuminated by studies on the embryos of model
organisms, there is an emerging focus on human embryonic development, and we have
expanded our coverage of the topic to include advances in studying early stages, an
outline of the development of the human placenta, and a box on human twinning. The
mechanisms involved in pattern formation in the early development of our vertebrate
model organisms are considered in Chapters 4 and 5. These chapters are organized as
in the previous edition, with the process of laying down the early body plan being first
described in its entirety in Xenopus (Chapter 4), the vertebrate in which the general
principles were discovered. This is followed by comparisons with the process in the
zebrafish (Chapter 4), and in chick and mouse (Chapter 5). Chapter 5 also considers
how the body plan is completed, which mainly rests on studies in chick and mouse
embryos. Chapter 6 focuses on pattern formation in two invertebrate model organisms,
the nematode and the sea urchin, with an online section on ascidian development.
Chapters 7 and 8 focus on the fundamental processes of morphogenesis and differ-
entiation, respectively, and have been extensively revised, with particular reference to
the role of planar cell polarity and convergent extension in Chapter 7, and the impact
of single-cell transcriptomics in dissecting cell-fate decisions, with the blood cell lin-
eages as an example, in Chapter 8. Chapter 8 also includes more extensive coverage of
the role of epigenetics in development and cell differentiation, and some new boxes,
including one describing organoids—three-dimensional organ cultures that mimic tis-
sues and organs—and their potential clinical uses. Chapter 9 deals with germ cells and
vi Preface

fertilization. Organogenesis (Chapter 10) and the development of the nervous system
(Chapter 11) are huge topics, so we have had to be very selective in our coverage, but
have included a new box in Chapter 10 on mammary gland development and its rel-
evance to understanding breast cancer. Sections of the chapter on the development of
the Drosophila tracheal system and the mammalian vascular system have been moved
to Chapter 7, and other sections from previous editions have been placed online.
Growth and regeneration are considered together in the same chapter (Chapter 12).
Chapter 13 deals with plant development. This chapter has been updated and includes
a new section on vernalization. The last chapter (Chapter 14) deals with development
in relation to evolution and has been reorganized and updated throughout, highlight-
ing the impact of genomics and the many insights it has brought to this aspect of
developmental biology. Evolution and development are inextricably linked in ways
we are only now beginning to understand, with the convergence of genomics and cell
biology on embryos. Together with the new technologies for gene editing, genomics is
rapidly expanding the range of species accessible to evolutionary studies.
We have assumed that students have some familiarity with basic cell and molecular
biology and genetics, but all key concepts, such as the control of gene activity, are
explained in the text. There is an extensive Glossary, which means that the book is
self-contained. The illustrations are a special feature and have been carefully designed
and chosen to illuminate both experiments and mechanisms. New diagrams and pho-
tographs are included throughout the book, together with information about their
sources. In providing further reading, our prime concern has been to guide the student
to particularly helpful papers and reviews, rather than to give credit to all the scientists
who have made major contributions: to those whom we have neglected, we apologize.
The main authors for this new edition are, as for the last edition, Lewis Wolpert,
Cheryll Tickle, and Alfonso Martinez Arias. We have bid farewell to co-authors of previ-
ous editions, Jim Smith, Elliot Meyerowitz, Elizabeth Robertson, and Andrew Lumsden,
and thank them for their pivotal contributions over several editions. The remaining
long-standing co-author, Peter Lawrence, has been joined by James Locke for this edi-
tion, who has revised the chapter on plants. Each chapter has also been reviewed by a
number of experts (see page xxv), to whom we are very grateful. The authors made the
initial revisions, which were then deciphered, edited, and incorporated by our editor,
Eleanor Lawrence, who has been helped for this edition by Amanda Tromans. We thank
them both. Eleanor’s involvement has been absolutely essential in the preparation of
this edition and her expertise and influence pervades the book. Her input has also been
invaluable in ensuring that the information in the book is readily accessible to students.
The new illustrations were brilliantly drawn or adapted by Matthew McClements, who
created the illustrations for the first and subsequent editions.
We are indebted to Roseanna Levermore and Jonathan Crowe at Oxford University
Press for their help and suggestions throughout the preparation of this new edition.

L. W.

London
October 2018

C. T.

Bath
October 2018

A. M. A.

Cambridge
October 2018
Learning from this book
Principles of Development includes a number of features to help make it easy to use, and to make your learning as effective as possible.
Experimental boxes discuss both classic and current experimental research,
demonstrating ‘how we know what we know.’
Cell Biology boxes equip you with a robust conceptual framework on which to
add further detail from the vast amount of scientific information available to us
today.
Medical boxes illustrate the direct relevance of developmental biology to medi-
cine and health-related issues.
Special interest boxes highlight topics of interest such as ‘The development of
the neural circuit for the knee-jerk reflex’ in Chapter 11 and the ‘Origins of mor-
phological diversity in dogs’ in Chapter 14.
Summary boxes provide a brief overview of each main section, which we hope
you will find particularly useful when revising for examinations. Summary boxes
are augmented by a bullet-point review of the chapter’s major concepts at the
end of each chapter.
EXPERIMENTAL BOX 8C Single-cell analysis of cell-fa
During development, differentiating cells progress from a multi
potent state towards terminally differentiated states, in which
they express a specific set of genes that are associated with
the specialized structure and function of the fully differentiated
cells. This progression is generally envisaged as a sequence o
CELL BIOLOGY BOX 4B The Wnt/β-catenin signaling pat
The important developmental
Wnt abs
signaling pathway initiated by
the Wnt family of intercellular
signaling proteins (pronounced LRP5/6
‘Wints’) is named after the proteins
MEDICAL BOX 11D Autism: a developmental disorder
The brain works through the release of neurotransmitter mol
ecules at synapses, which interconnect neurons in highly com
plex networks. Correct synapse formation and refinement during
development is therefore of crucial importance to cognitive func
tion. Autism is a common (1 in around 120 live births) and per
BOX 11C The development of the neural circuit for the
Neural circuit that underlies the knee-jerk reflex
dorsal root sensory muscle quadriceps
neuron spindle
spinal
SUMMARY
Transcriptional control is a key feature of cell differentiation. Tis
sion of a eukaryotic gene depends on control elements located
regions flanking the gene. These elements comprise both the
adjacent to the start site of transcription, which bind RNA po
distant elements such as enhancers that control tissue-specifi
stage specific gene expression The combination of different
viii Learning from this book

Online resources

The online resources that accompany this text contain additional teaching and learning
resources for both lecturers and students.
Visit the site at www.oup.com/uk/wolpert6e

For students

Flashcard glossary

Flashcards, which can be downloaded your mobile phone, help you to test your recall
of key terminology.

Multiple-choice questions

Use the extensive bank of multiple-choice questions to check your understanding of

concepts introduced in the book, and get instant feedback on your progress.

Answer guidance

The authors have written answer guidance to the long-answer questions found at the
end of each chapter, so you can check that you have considered all the appropriate
points when responding to each question.

Web links and web activities

Links to websites, with notes to explain how each site relates to concepts featured in
the book, are provided to help you explore topics in the book in more detail. Complete
the associated activities to get to grips with the material in a hands-on way.

In silico practicals

In the textbook, we set out the current understanding of developmental processes

and provide some examples of ‘how we know what we know’ in experimental boxes.
However, it is impossible to present the raw data that provide the evidence on which
our knowledge is based. The purpose of the practicals is to give you the opportunity
to examine raw data and appreciate the way in which results are interpreted and lead
to advances in understanding. The in silico practicals include questions to help you
think more deeply about the material you have learned.

Movies from real research

The movies show key developmental processes occurring in real embryos, to help you
visualize the processes of developmental biology as they unfold in three dimensions.

Signaling pathway animations

Custom-made animations of key signaling pathways break down these complex pro-
cesses into stages, making them easier to understand and remember.
 Learning from this book ix

Online extracts

Online extracts provide additional information on a range of extra topics, including:

● P-element-mediated transformation
● Genetic mosaics and mitotic recombination
● Kidney development
● Development of the Drosophila compound eye
● Reaction–diffusion mechanisms (extended version)
● How the bird wing evolved
● Ascidians
● Directed dilation
● Chromosome capture techniques

For registered adopters

Electronic artwork

Figures from the book are available to download, for use in lecture slides.

Journal clubs

Journal clubs consist of discussion questions focused around primary literature arti-
cles that relate to topics featured in the book. Use these as an additional learning tool
to help your students become more adept at assimilating knowledge from the research
literature.

Test bank

A test bank of questions is available for you to use when assessing your students.
About the authors
Lewis Wolpert is Emeritus Professor of Biology as Applied to Medicine, in the
Department of Anatomy and Developmental Biology, University College London,
London, UK. He is the author of The Triumph of the Embryo, A Passion for Science,
The Unnatural Nature of Science, and Six Impossible Things Before Breakfast.

Cheryll Tickle is Emeritus Professor in the Department of Biology and Biochemistry,

University of Bath, Bath, UK.

Alfonso Martinez Arias is Professor of Developmental Mechanick at the University

of Cambridge, UK.

Peter Lawrence is in the Department of Zoology, University of Cambridge, UK, and

Emeritus member of the Medical Research Council Laboratory of Molecular Biology,
Cambridge, UK. He is the author of The Making of a Fly.

James Locke is Royal Society University Research Fellow and Research Group Leader
in the Sainsbury Laboratory, University of Cambridge, UK, where he examines noise
in gene regulation.

Eleanor Lawrence is a freelance science writer and editor.

Matthew McClements is an illustrator who specializes in design for scientific, techni-

cal, and medical communication.
Summary of contents
Preface  v

Learning from this book  vii

About the authors  x

List of boxes  xxiii

Reviewer acknowledgments  xxv

Chapter 1 History and basic concepts 1

Chapter 2 Development of the Drosophila body plan 37

Chapter 3 Vertebrate development I: life cycles and experimental

techniques94

Chapter 4 Vertebrate development II: Xenopus and zebrafish 142

Chapter 5 Vertebrate development III: chick and mouse—completing

the body plan 183

Chapter 6 Development of nematodes and sea urchins 235

Chapter 7 Morphogenesis: change in form in the early embryo 271

Chapter 8 Cell differentiation and stem cells 333

Chapter 9 Germ cells, fertilization, and sex determination 397

Chapter 10 Organogenesis435

Chapter 11 Development of the nervous system 505

Chapter 12 Growth, post-embryonic development, and regeneration 553

Chapter 13 Plant development 609

Chapter 14 Evolution and development 651

Glossary 702

Index 725
Contents

Preface  v 1.13 Inductive interactions make cells different from

each other 24
Learning from this book  vii
■■ Cell Biology Box 1E Signal transduction and intracellular
About the authors  x signaling pathways 26
List of boxes  xxiii 1.14 The response to inductive signals depends on the
state of the cell 26
Reviewer acknowledgments  xxv
1.15 Patterning can involve the interpretation of positional
information27
Chapter 1 History and basic concepts 1 ■■ Medical Box 1F When development goes awry 28
The origins of developmental biology3 1.16 Lateral inhibition can generate spacing patterns 30
1.1 Aristotle first defined the problem of epigenesis versus 1.17 Localization of cytoplasmic determinants and asymmetric
preformation3 cell division can make daughter cells different from each other 30
■■ Box 1A Basic stages of Xenopus laevis development 4 1.18 The embryo contains a generative rather than
1.2 Cell theory changed how people thought about a descriptive program 32
embryonic development and heredity 4 1.19 The reliability of development is achieved by various
1.3 Two main types of development were originally proposed 6 means32

■■ Cell Biology Box 1B The mitotic cell cycle 7 1.20 The complexity of embryonic development is due
to the complexity of cells themselves 33
1.4 The discovery of induction showed that one group of
cells could determine the development of neighboring cells 8 1.21 Development is a central element in evolution 33

1.5 Developmental biology emerged from the coming together Summary34

of genetics and embryology 8 Summary to Chapter 1 35
1.6 Development is studied mainly through selected model
organisms9 Chapter 2 Development of the Drosophila
1.7 The first developmental genes were identified as body plan 37
spontaneous mutations 11 Drosophila life cycle and overall development38
Summary 13 2.1 The early Drosophila embryo is a multinucleate
A conceptual tool kit13 syncytium38
1.8 Development involves the emergence of pattern, change in 2.2 Cellularization is followed by gastrulation and
form, cell differentiation, and growth 14 segmentation40
■■ Cell Biology Box 1C Germ layers 15 2.3 After hatching, the Drosophila larva develops through
1.9 Cell behavior provides the link between gene action and several larval stages, pupates, and then undergoes
developmental processes 17 metamorphosis to become an adult 41

1.10 Genes control cell behavior by specifying which 2.4 Many developmental genes were identified in Drosophila
proteins are made 17 through large-scale genetic screening for induced mutations 42

1.11 The expression of developmental genes is under ■■ Experimental Box 2A Mutagenesis and genetic screening

tight control 19 strategy for identifying developmental mutants in Drosophila 43

■■ Experimental Box 1D Visualizing gene expression Summary44

in embryos 20 Setting up the body axes44
1.12 Development is progressive and the fates of cells 2.5 The body axes are set up while the Drosophila embryo
become determined at different times 22 is still a syncytium 45
xiv Contents

2.6 Maternal factors set up the body axes and direct the Summary75
early stage of Drosophila development 46 Segmentation genes and segment patterning75
2.7 Three classes of maternal genes specify the 2.23 Expression of the engrailed gene defines the boundary
antero-posterior axis 47 of a parasegment, which is also a boundary of cell lineage
2.8 Bicoid protein provides an antero-posterior gradient of a restriction76
morphogen48 2.24 Segmentation genes stabilize parasegment boundaries 77
2.9 The posterior pattern is controlled by the gradients 2.25 Signals generated at the parasegment boundary delimit
of Nanos and Caudal proteins 50 and pattern the future segments 78
2.10 The anterior and posterior extremities of the embryo ■■ Cell Biology Box 2E The Hedgehog signaling pathway 80
are specified by activation of a cell-surface receptor 51
■■ Experimental Box 2F Mutants in denticle pattern provided
2.11 The dorso-ventral polarity of the embryo is specified by clues to the logic of segment patterning 81
localization of maternal proteins in the egg vitelline envelope 52
Summary83
2.12 Positional information along the dorso-ventral axis
Specification of segment identity83
is provided by the Dorsal protein 53
2.26 Segment identity in Drosophila is specified by Hox genes 84
■■ Cell Biology Box 2B The Toll signaling pathway: a
multifunctional pathway 54 2.27 Homeotic selector genes of the bithorax complex are
responsible for diversification of the posterior segments 85
Summary54
2.28 The Antennapedia complex controls specification
Localization of maternal determinants during oogenesis55
of anterior regions 86
2.13 The antero-posterior axis of the Drosophila egg is
2.29 The order of Hox gene expression corresponds to the
specified by signals from the preceding egg chamber and by
order of genes along the chromosome 87
interactions of the oocyte with follicle cells 56
2.30 The Drosophila head region is specified by genes other
■■ Cell Biology Box 2C The JAK–STAT signaling pathway 58
than the Hox genes 87
2.14 Localization of maternal mRNAs to either end of the egg
Summary88
depends on the reorganization of the oocyte cytoskeleton 58
Summary to Chapter 289
2.15 The dorso-ventral axis of the egg is specified by
movement of the oocyte nucleus followed by signaling
Chapter 3 Vertebrate development I: life cycles
between oocyte and follicle cells 60
and experimental techniques 94
Summary61
Vertebrate life cycles and outlines of development95
Patterning the early embryo62
3.1 The frog Xenopus laevis is the model amphibian for
2.16 The expression of zygotic genes along the dorso-ventral studying development of the body plan 98
axis is controlled by Dorsal protein 62
3.2 The zebrafish embryo develops around a large mass
2.17 The Decapentaplegic protein acts as a morphogen to of yolk 102
pattern the dorsal region 64
3.3 Birds and mammals resemble each other and differ from
2.18 The antero-posterior axis is divided up into broad Xenopus in some important features of early development 105
regions by gap gene expression 66
3.4 The early chicken embryo develops as a flat disc of cells
2.19 Bicoid protein provides a positional signal for the overlying a massive yolk 106
anterior expression of zygotic hunchback67
3.5 The mouse egg has no yolk and early development
2.20 The gradient in Hunchback protein activates and involves the allocation of cells to form the placenta and
represses other gap genes 68 extra-embryonic membranes 110
■■ Experimental Box 2D Targeted gene expression and Experimental approaches to studying vertebrate
misexpression screening 69 development115
Summary70 3.6 Gene expression in embryos can be mapped by in situ
Activation of the pair-rule genes and the establishment nucleic acid hybridization 116
of parasegments71 ■■ Experimental Box 3A Gene-expression profiling by DNA
2.21 Parasegments are delimited by expression of pair-rule microarrays and RNA seq 117
genes in a periodic pattern 71 3.7 Fate mapping and lineage tracing reveal which cells
2.22 Gap gene activity positions stripes of pair-rule gene in which parts of the early embryo give rise to particular
expression73 adult structures 118
 Contents xv

3.8 Not all techniques are equally applicable to all vertebrates 120
3.9 Developmental genes can be identified by spontaneous
mutation and by large-scale mutagenesis screens 121
■■ Experimental Box 3B Large-scale mutagenesis screens
for recessive mutations in zebrafish 123
3.10 Transgenic techniques enable animals to be produced
with mutations in specific genes 124
■■ Experimental Box 3C The Cre/loxP system: a strategy
for making gene knock-outs in mice 127
4.7 Mesoderm induction occurs during a limited period in the
blastula stage 155
4.8 Zygotic gene expression is turned on at the mid-blastula
transition156
4.9 Mesoderm-inducing and patterning signals are produced
by the vegetal region, the organizer, and the ventral mesoderm 157
4.10 Members of the TGF-β family have been identified as
mesoderm inducers 158
■■ Experimental Box 4D Investigating receptor function using

■■ Experimental Box 3D The CRISPR-Cas9 genome-editing dominant-negative proteins 159

system128 4.11 The zygotic expression of mesoderm-inducing and
3.11 Gene function can also be tested by transient patterning signals is activated by the combined actions
transgenesis and gene silencing 130 of maternal VegT and Wnt signaling 159

Human embryonic development131 4.12 Threshold responses to gradients of signaling proteins

are likely to pattern the mesoderm 161
3.12 The early development of a human embryo is similar
to that of the mouse 131 Summary162

■■ Medical Box 3E Preimplantation genetic diagnosis 134 The Spemann organizer and neural induction163

3.13 The timing of formation and the anatomy of the ■■ Cell Biology Box 4E The fibroblast growth factor

human placenta differs from that in the mouse 135 signaling pathway 163

3.14 Some studies of human development are possible 4.13 Signals from the organizer pattern the mesoderm
but are subject to strict laws 136 dorso-ventrally by antagonizing the effects of ventral signals 164

■■ Box 3F Identical twins 137 4.14 The antero-posterior axis of the embryo emerges during
gastrulation165
Summary to Chapter 3 138
4.15 The neural plate is induced in the ectoderm 168
Chapter 4 Vertebrate development II: Xenopus 4.16 The nervous system is patterned along the
and zebrafish 142 antero-posterior axis by signals from the mesoderm 170
Setting up the body axes143 4.17 The final body plan emerges by the end of gastrulation
4.1 The animal–vegetal axis is maternally determined and neurulation 171
in Xenopus143 Summary172
■■ Cell Biology Box 4A Intercellular protein signals Development of the body plan in zebrafish172
in vertebrate development 145 4.18 The body axes in zebrafish are established by maternal
■■ Cell Biology Box 4B The Wnt/β-catenin signaling pathway 146 determinants173
4.2 Local activation of Wnt/β-catenin signaling specifies 4.19 The germ layers are specified in the zebrafish blastoderm
the future dorsal side of the embryo 147 by similar signals to those in Xenopus173
4.3 Signaling centers develop on the dorsal side of the 4.20 The shield in zebrafish is the embryonic organizer 176
blastula149 ■■ Box 4F A zebrafish gene regulatory network 176
Summary150 Summary to Chapter 4 178
The origin and specification of the germ layers150
4.4 The fate map of the Xenopus blastula makes clear Chapter 5 Vertebrate development III: chick and
the function of gastrulation 151 mouse—completing the body plan 183
4.5 Cells of the early Xenopus embryo do not yet have their Development of the body plan in chick and mouse and
fates determined and regulation is possible 152 ­generation of the spinal cord184
4.6 Endoderm and ectoderm are specified by maternal 5.1 The antero-posterior polarity of the chick blastoderm is
factors, whereas mesoderm is induced from ectoderm by related to the primitive streak 184
signals from the vegetal region 152
5.2 Early stages in mouse development establish separate
■■ Cell Biology Box 4C Signaling by members of the TGF-β cell lineages for the embryo and the extra-embryonic
family of growth factors 155 structures186
xvi Contents

5.3 Movement of the anterior visceral endoderm indicates Chapter 6 Development of nematodes and
the definitive antero-posterior axis in the mouse embryo 190 sea urchins 235
5.4 The fate maps of vertebrate embryos are variations on Nematodes236
a basic plan 192 ■■ Cell Biology Box 6A Apoptotic pathways in nematodes,
■■ Cell Biology Box 5A Fine-tuning Nodal signaling 193 Drosophila, and mammals 238
5.5 Mesoderm induction and patterning in the chick 6.1 The cell lineage of Caenorhabditis elegans is
and mouse occurs during primitive streak formation 195 largely invariant 239
5.6 The node that develops at the anterior end of the streak 6.2 The antero-posterior axis in Caenorhabditis elegans is
in chick and mouse embryos is equivalent to the Spemann determined by asymmetric cell division 239
organizer in Xenopus196 ■■ Experimental Box 6B Gene silencing by antisense RNA
5.7 Neural induction in chick and mouse is initiated by FGF and RNA interference 241
signaling with inhibition of BMP signaling being required in 6.3 The dorso-ventral axis in Caenorhabditis elegans is
a later step 198 determined by cell–cell interactions 242
■■ Cell Biology Box 5B Chromatin-remodeling complexes 201 6.4 Both asymmetric divisions and cell–cell interactions
5.8 Axial structures in chick and mouse are generated from specify cell fate in the early nematode embryo 245
self-renewing cell populations 202 6.5 Cell differentiation in the nematode is closely linked
Summary204 to the pattern of cell division 246
Somite formation and antero-posterior patterning205 6.6 Hox genes specify positional identity along the
■■ Cell Biology Box 5C Retinoic acid: a small-molecule antero-posterior axis in Caenorhabditis elegans 247
intercellular signal 206 6.7 The timing of events in nematode development is under
5.9 Somites are formed in a well-defined order along genetic control that involves microRNAs 248
the antero-posterior axis 206 ■■ Box 6C Gene silencing by microRNAs 250
■■ Cell Biology Box 5D The Notch signaling pathway 211 6.8 Vulval development is initiated through the induction of
5.10 Identity of somites along the antero-posterior axis is a small number of cells by short-range signals from a single
specified by Hox gene expression 213 inducing cell 251

■■ Box 5E The Hox genes 214 Summary253

5.11 Deletion or overexpression of Hox genes causes Echinoderms254

changes in axial patterning 217 6.9 The sea urchin embryo develops into a free-swimming
5.12 Hox gene expression is activated in an anterior larva255
to posterior pattern 219 6.10 The sea urchin egg is polarized along the
5.13 The fate of somite cells is determined by signals from animal–vegetal axis 256
the adjacent tissues 221 6.11 The sea urchin fate map is finely specified, yet
Summary223 considerable regulation is possible 257

The origin and patterning of neural crest223 6.12 The vegetal region of the sea urchin embryo acts
as an organizer 258
5.14 Neural crest cells arise from the borders of the neural plate
and migrate to give rise to a wide range of different cell types 223 6.13 The sea urchin vegetal region is demarcated by the
nuclear accumulation of β-catenin260
5.15 Neural crest cells migrate from the hindbrain to populate
the branchial arches 225 6.14 The animal–vegetal axis and the oral–aboral
axis can be considered to correspond to the
Summary226
antero-posterior and dorso-ventral axes of other
Determination of left–right asymmetry227 deuterostomes261
5.16 The bilateral symmetry of the early embryo is broken 6.15 The pluteus skeleton develops from the primary
to produce left–right asymmetry of internal organs 227 mesenchyme262
5.17 Left–right symmetry breaking may be initiated within 6.16 The oral–aboral axis in sea urchins is related to the
cells of the early embryo 229 plane of the first cleavage 263
Summary230 6.17 The oral ectoderm acts as an organizing region for
Summary to Chapter 5 230 the oral–aboral axis 264
 Contents xvii

■■ Experimental Box 6D The gene regulatory network for 7.15 Gastrulation in chick and mouse embryos involves the
sea urchin endomesoderm specification 265 separation of individual cells from the epiblast and their
Summary266 ingression through the primitive streak 306

Summary to Chapter 6 267 Summary309

Neural tube formation311
Chapter 7 Morphogenesis: change in form in 7.16 Neural tube formation is driven by changes in cell
the early embryo 271 shape and convergent extension 311
Cell adhesion273 ■■ Cell Biology Box 7D Eph receptors and their ephrin ligands 313
■■ Cell Biology Box 7A Cell-adhesion molecules and cell ■■ Medical Box 7E Neural tube defects 314
junctions274
Summary315
7.1 Sorting out of dissociated cells demonstrates differences
Formation of tubes and branching morphogenesis316
in cell adhesiveness in different tissues 275
7.17 The Drosophila tracheal system is a prime example of
7.2 Cadherins can provide adhesive specificity 276
branching morphogenesis 316
7.3 The activity of the cytoskeleton regulates the mechanical
7.18 The vertebrate vascular system develops by
properties of cells and their interactions with each other 277
vasculogenesis followed by sprouting angiogenesis 318
■■ Cell Biology Box 7B The cytoskeleton, cell-shape change,
7.19 New blood vessels are formed from pre-existing
and cell movement 278
vessels in angiogenesis 319
7.4 Transitions of tissues from an epithelial to a mesenchymal
Summary320
state, and vice versa, involve changes in adhesive junctions 279
Cell migration320
Summary280
7.20 Embryonic neural crest gives rise to a wide range
Cleavage and formation of the blastula280
of different cell types 321
7.5 The orientation of the mitotic spindle determines the
7.21 Neural crest migration is controlled by
plane of cleavage at cell division 281
environmental cues 321
7.6 The positioning of the spindle within the cell also
7.22 The formation of the lateral-line primordium in
determines whether daughter cells will be the same or different
fishes is an example of collective cell migration 323
sizes283
7.23 Body wall closure occurs in Drosophila, Caenorhabditis,
7.7 Cells become polarized in the sea urchin blastula and
mammals, and chick 324
the mouse morula 285
Summary325
7.8 Fluid accumulation as a result of tight-junction
formation and ion transport forms the blastocoel of Summary to Chapter 7 326
the mammalian blastocyst 287
Summary288 Chapter 8 Cell differentiation and stem cells 333
Gastrulation movements289 ■■ Box 8A Conrad Waddington’s ‘epigenetic landscape’
provides a framework for thinking about how cells differentiate 335
7.9 Gastrulation in the sea urchin involves an epithelial-to-
mesenchymal transition, cell migration, and invagination of the The control of gene expression337
blastula wall 289 8.1 Control of transcription involves both general and
7.10 Mesoderm invagination in Drosophila is due to changes tissue-specific transcriptional regulators 338
in cell shape controlled by genes that pattern the 8.2 Gene expression is also controlled by epigenetic chemical
dorso-ventral axis 293 modifications to DNA and histone proteins that alter chromatin
7.11 Germ-band extension in Drosophila involves myosin- structure341
dependent remodeling of cell junctions and cell intercalation 295 ■■ Cell Biology Box 8B Epigenetic control of gene expression

7.12 Planar cell polarity confers directionality on a tissue 296 by chromatin modification 344

7.13 Gastrulation in amphibians and fish involves involution, 8.3 Patterns of gene activity can be inherited by persistence
epiboly, and convergent extension 299 of gene-regulatory proteins or by maintenance of chromatin
modifications347
■■ Box 7C Convergent extension 302
8.4 Changes in patterns of gene activity during differentiation can
7.14 Xenopus notochord development illustrates the
be triggered by extracellular signals 348
dependence of medio-lateral cell elongation and cell
intercalation on a pre-existing antero-posterior polarity 305 Summary349
xviii Contents

Cell differentiation and stem cells350 Chapter 9 Germ cells, fertilization,

8.5 Muscle differentiation is determined by the MyoD family and sex determination 397
of transcription factors 350 The development of germ cells398
8.6 The differentiation of muscle cells involves withdrawal 9.1 Germ cell fate is specified in some embryos by a distinct
from the cell cycle, but is reversible 352 germplasm in the egg 399
8.7 All blood cells are derived from multipotent stem cells 354 9.2 In mammals germ cells are induced by cell–cell interactions
8.8 Intrinsic and extrinsic changes control differentiation of during development 401
the hematopoietic lineages 357 9.3 Germ cells migrate from their site of origin to the gonad 402
■■ Experimental Box 8C Single-cell analysis of cell-fate 9.4 Germ cells are guided to their destination by
decisions358 chemical signals 403
8.9 Developmentally regulated globin gene expression is 9.5 Germ cell differentiation involves a halving of
controlled by control regions far distant from the coding chromosome number by meiosis 404
regions361 ■■ Box 9A Polar bodies 405
8.10 The epidermis of adult mammalian skin is continually 9.6 Oocyte development can involve gene amplification
being replaced by derivatives of stem cells 363 and contributions from other cells 408
■■ Medical Box 8D Treatment of junctional epidermolysis 9.7 Factors in the cytoplasm maintain the totipotency of the egg 408
bullosa with skin grown from genetically corrected
9.8 In mammals some genes controlling embryonic growth
stem cells 366
are ‘imprinted’ 409
8.11 Stem cells use different modes of division to maintain
Summary412
tissues367
Fertilization412
8.12 The lining of the gut is another epithelial tissue
that requires continuous renewal 368 9.9 Fertilization involves cell-surface interactions between
egg and sperm 413
8.13 Skeletal muscle and neural cells can be renewed
from stem cells in adults 370 9.10 Changes in the egg plasma membrane and enveloping
layers at fertilization block polyspermy 415
8.14 Embryonic stem cells can proliferate and differentiate
into many cell types in culture and contribute to normal 9.11 Sperm–egg fusion causes a calcium wave that results
development in vivo 372 in egg activation 416

■■ Experimental Box 8E The derivation and culture of mouse Summary418

embryonic stem cells 374 Determination of the sexual phenotype419
Summary375 9.12 The primary sex-determining gene in mammals is on
The plasticity of the differentiated state376 the Y chromosome 419

8.15 Nuclei of differentiated cells can support development 376 9.13 Mammalian sexual phenotype is regulated by gonadal
hormones420
8.16 Patterns of gene activity in differentiated cells can be
changed by cell fusion 378 9.14 The primary sex-determining factor in Drosophila is the
number of X chromosomes and is cell autonomous 422
8.17 The differentiated state of a cell can change by
transdifferentiation379 9.15 Somatic sexual development in Caenorhabditis is
determined by the number of X chromosomes 424
8.18 Adult differentiated cells can be reprogrammed to form
pluripotent stem cells 381 9.16 Determination of germ cell sex depends on both genetic
constitution and intercellular signals 425
■■ Experimental Box 8F Induced pluripotent stem cells 382
9.17 Various strategies are used for dosage compensation of
8.19 Stem cells could be a key to regenerative medicine 382
X-linked genes 427
■■ Experimental Box 8G Stem cells can be cultured in vitro
Summary429
to produce ‘organoids’—structures that mimic tissues and
organs386 Summary to Chapter 9 431

8.20 Various approaches can be used to generate

Chapter 10 Organogenesis435
differentiated cells for cell-replacement therapies 388
The insect wing and leg436
Summary391
10.1 Imaginal discs arise from the ectoderm in the
Summary to Chapter 8 391
early Drosophila embryo 437
 Contents xix

10.2 Imaginal discs arise across parasegment boundaries 10.20 Self-organization may be involved in the
and are patterned by signaling at compartment boundaries 438 development of the limb 475
10.3 The adult wing emerges at metamorphosis after folding ■■ Box 10E Reaction–diffusion mechanisms 476
and evagination of the wing imaginal disc 439 10.21 Limb muscle is patterned by the connective tissue 477
10.4 A signaling center at the boundary between anterior 10.22 The initial development of cartilage, muscles, and
and posterior compartments patterns the Drosophila wing tendons is autonomous 478
disc along the antero-posterior axis 440
10.23 Joint formation involves secreted signals and
■■ Box 10A Positional information and morphogen gradients 443 mechanical stimuli 478
10.5 A signaling center at the boundary between dorsal 10.24 Separation of the digits is the result of programmed
and ventral compartments patterns the Drosophila wing cell death 479
along the dorso-ventral axis 445
Summary480
10.6 Vestigial is a key regulator of wing development that
Teeth481
acts to specify wing identity and control wing growth 445
10.25 Tooth development involves epithelial–mesenchymal
10.7 The Drosophila wing disc is also patterned along
interactions and a homeobox gene code specifies tooth identity 482
the proximo-distal axis 447
Summary484
10.8 The leg disc is patterned in a similar manner to the
wing disc, except for the proximo-distal axis 448 Vertebrate lungs484

10.9 Different imaginal discs can have the same 10.26 The vertebrate lung develops from a bud of endoderm 484
positional values 450 ■■ Medical Box 10F What developmental biology can teach

Summary450 us about breast cancer 486

The vertebrate limb452 10.27 Morphogenesis of the lung involves three modes of
branching488
10.10 The vertebrate limb develops from a limb bud and its
development illustrates general principles 452 Summary489

10.11 Genes expressed in the lateral plate mesoderm The vertebrate heart489
are involved in specifying limb position, polarity, and identity 454 10.28 The development of the vertebrate heart involves
10.12 The apical ectodermal ridge is required for limb-bud morphogenesis and patterning of a mesodermal tube 489
outgrowth and the formation of structures along the proximo- The vertebrate eye492
distal axis of the limb 457 10.29 Development of the vertebrate eye involves
10.13 Formation and outgrowth of the limb bud involves interactions between an extension of the forebrain and
oriented cell behavior 458 the ectoderm of the head 493
10.14 Positional value along the proximo-distal axis of Summary497
the limb bud is specified by a combination of graded signaling Summary to Chapter 10 497
and a timing mechanism 460
10.15 The polarizing region specifies position along the limb’s Chapter 11 Development of the nervous system 505
antero-posterior axis 462 Specification of cell identity in the nervous system507
10.16 Sonic hedgehog is the polarizing region morphogen 464 11.1 Initial regionalization of the vertebrate brain involves
■■ Medical Box 10B Too many fingers: mutations that affect signals from local organizers 507
antero-posterior patterning can cause polydactyly 465 11.2 Local signaling centers pattern the brain along the
■■ Cell Biology Box 10C Sonic hedgehog signaling and the antero-posterior axis 508
primary cilium 466 11.3 The cerebral cortex is patterned by signals from the
10.17 The dorso-ventral axis of the limb is controlled by the anterior neural ridge 509
ectoderm468 11.4 The hindbrain is segmented into rhombomeres by
■■ Medical Box 10D Teratogens and the consequences of boundaries of cell-lineage restriction 509
damage to the developing embryo 470 11.5 Hox genes provide positional information in the
10.18 Development of the limb is integrated by interactions developing hindbrain 512
between signaling centers 470 11.6 The pattern of differentiation of cells along the
10.19 Hox genes have multiple inputs into the patterning dorso-ventral axis of the spinal cord depends on ventral
of the limbs 472 and dorsal signals 513
xx Contents

11.7 Neuronal subtypes in the ventral spinal cord are Chapter 12 Growth, post-embryonic development,
specified by the ventral to dorsal gradient of Shh 515 and regeneration 553
11.8 Spinal cord motor neurons at different dorso-ventral Growth554
positions project to different trunk and limb muscles 516 12.1 Tissues can grow by cell proliferation, cell enlargement,
11.9 Antero-posterior pattern in the spinal cord is or accretion 555
determined in response to secreted signals from the node 12.2 Cell proliferation is controlled by regulating entry into
and adjacent mesoderm 517 the cell cycle 556
Summary518 12.3 Cell division in early development can be controlled
The formation and migration of neurons518 by an intrinsic developmental program 557
11.10 Neurons in Drosophila arise from proneural clusters 519 12.4 Extrinsic signals coordinate cell division, cell growth,
11.11 The development of neurons in Drosophila involves and cell death in the developing Drosophila wing 558
asymmetric cell divisions and timed changes in gene ■■ Cell Biology Box 12A The core Hippo signaling pathways in
expression521 Drosophila and mammals 559
11.12 The production of vertebrate neurons involves lateral 12.5 Cancer can result from mutations in genes that control
inhibition, as in Drosophila522 cell proliferation 560
■■ Box 11A Specification of the sensory organs of 12.6 The relative contributions of intrinsic and extrinsic
adult Drosophila523 factors in controlling size differ in different mammalian organs 562
11.13 Neurons are formed in the proliferative zone of the 12.7 Overall body size depends on the extent and the
vertebrate neural tube and migrate outwards 524 duration of growth 564
■■ Experimental Box 11B Timing the birth of cortical 12.8 Hormones and growth factors coordinate the growth of
neurons526 different tissues and organs and contribute to determining
11.14 Many cortical interneurons migrate tangentially 528 overall body size 565

Summary528 12.9 Elongation of the long bones illustrates how growth

can be determined by a combination of an intrinsic growth
Axon navigation529
program and extracellular factors 566
11.15 The growth cone controls the path taken by a
■■ Box 12B Digit length ratio is determined in the embryo 568
growing axon 530
12.10 The amount of nourishment an embryo receives can
■■ Box 11C The development of the neural circuit for
have profound effects in later life 570
the knee-jerk reflex 532
Summary571
11.16 Motor neuron axons in the chick limb are guided
by ephrin–Eph interactions 533 Molting and metamorphosis572

11.17 Axons crossing the midline are both attracted 12.11 Arthropods have to molt in order to grow 572
and repelled 534 12.12 Insect body size is determined by the rate and
11.18 Neurons from the retina make ordered connections duration of larval growth 573
with visual centers in the brain 535 12.13 Metamorphosis in amphibians is under hormonal
Summary538 control575

Synapse formation and refinement539 Summary576

11.19 Synapse formation involves reciprocal interactions 539 Regeneration577

11.20 Many motor neurons die during normal development 542 12.14 Regeneration involves repatterning of existing
tissues and/or growth of new tissues 578
■■ Medical Box 11D Autism: a developmental disorder that
involves synapse dysfunction 543 12.15 Amphibian limb regeneration involves cell
dedifferentiation and new growth 578
11.21 Neuronal cell death and survival involve both intrinsic
and extrinsic factors 544 ■■ Box 12C Regeneration in Hydra580

11.22 The map from eye to brain is refined by neural ■■ Box 12D Planarian regeneration 582
activity545 12.16 Limb regeneration in amphibians depends on the
Summary546 presence of nerves 586

Summary to Chapter 11 547 12.17 The limb blastema gives rise to structures with
positional values distal to the site of amputation 587
 Contents xxi

12.18 Retinoic acid can change proximo-distal positional
values in regenerating limbs 589
12.19 Mammals can regenerate the tips of the digits 590
12.20 Insect limbs intercalate positional values by both
proximo-distal and circumferential growth 591
■■ Box 12E Why can’t we regenerate our limbs? 592
13.12 The regular arrangement of leaves on a stem is
generated by regulated auxin transport 629
13.13 The outgrowth of secondary shoots is under
hormonal control 630
13.14 Root tissues are produced from Arabidopsis root apical
meristems by a highly stereotyped pattern of cell divisions 633

12.21 Heart regeneration in zebrafish involves the 13.15 Root hairs are specified by a combination
resumption of cell division by cardiomyocytes 594 of positional information and lateral inhibition 635

Summary596 Summary636

Aging and senescence597 Flower development and control of flowering636

12.22 Genes can alter the timing of senescence 598 13.16 Homeotic genes control organ identity in the flower 637

12.23 Cell senescence blocks cell proliferation 600 ■■ Box 13C The basic model for the patterning of the
Arabidopsis flower 639
12.24 Elimination of senescent cells in adult salamanders
explains why regenerative ability does not diminish with age 601 13.17 The Antirrhinum flower is patterned dorso-ventrally,
as well as radially 640
Summary602
13.18 The internal meristem layer can specify floral
Summary to Chapter 12 602
meristem patterning 641

Chapter 13 Plant development 609 13.19 The transition of a shoot meristem to a floral
meristem is under environmental and genetic control 642
13.1 The model plant Arabidopsis thaliana has a short life
cycle and a small diploid genome 611 ■■ Box 13D The circadian clock coordinates plant growth and
development643
Embryonic development612
13.20 Vernalization reflects the epigenetic memory of winter 643
13.2 Plant embryos develop through several distinct stages 612
13.21 Most flowering plants are hermaphrodites, but
■■ Box 13A Angiosperm embryogenesis 614
some produce unisexual flowers 645
13.3 Gradients of the signal molecule auxin establish the
Summary646
embryonic apical–basal axis 616
Summary to Chapter 13 647
13.4 Plant somatic cells can give rise to embryos
and seedlings 617
Chapter 14 Evolution and development 651
13.5 Cell enlargement is a major process in plant growth
■■ Box 14A Darwin’s finches 654
and morphogenesis 619
The evolution of development655
■■ Experimental Box 13B Plant transformation and
genome editing 620 14.1 Multicellular organisms evolved from single-celled
ancestors655
Summary621
14.2 Genomic evidence is throwing light on the evolution
Meristems622
of animals 657
13.6 A meristem contains a small, central zone of
■■ Box 14B The metazoan family tree 658
self-renewing stem cells 623
14.3 How gastrulation evolved is not known 659
13.7 The size of the stem cell area in the meristem is kept
constant by a feedback loop to the organizing center 623 14.4 More general characteristics of the body plan develop
earlier than specializations 660
13.8 The fate of cells from different meristem layers can be
changed by changing their position 624 14.5 Embryonic structures have acquired new functions
during evolution 661
13.9 A fate map for the embryonic shoot meristem can
be deduced using clonal analysis 626 14.6 Evolution of different types of eyes in different animal
groups is an example of parallel evolution 663
13.10 Meristem development is dependent on signals
from other parts of the plant 627 Summary664

13.11 Gene activity patterns the proximo-distal and The diversification of body plans665
adaxial–abaxial axes of leaves developing from the 14.7 Hox gene complexes have evolved through gene
shoot meristem 628 duplication665
xxii Contents

14.8 Differences in Hox gene expression determine the 14.15 Adaptive evolution within the same species provides
variation in position and type of paired appendages a way of studying the developmental basis for evolutionary
in arthropods 667 change684
14.9 Changes in Hox gene expression and their target ■■ Experimental Box 14D Pelvic reduction in sticklebacks
genes contributed to the evolution of the vertebrate is based on mutations in a gene control region 686
axial skeleton 671 Summary687
14.10 The basic body plan of arthropods and vertebrates Changes in the timing of developmental processes687
is similar, but the dorso-ventral axis is inverted 672
14.16 Changes in growth can modify the basic body plan 687
Summary673
■■ Box 14E Origins of morphological diversity in dogs 689
The evolutionary modification of specialized characters674
14.17 Evolution can be due to changes in the timing of
14.11 Limbs evolved from fins 674 developmental events 690
14.12 Limbs have evolved to fulfill different specialized functions 14.18 The evolution of life histories has implications for
678 development692
14.13 The evolution of limblessness in snakes is associated ■■ Box 14F Long- and short-germ development in insects 693
with changes in axial gene expression and mutations in a
Summary695
limb-specific enhancer 679
Summary to Chapter 14 696
14.14 Butterfly wing markings have evolved by
redeployment of genes previously used for other functions 680
■■ Experimental Box 14C Using CRISPR-Cas9 genome-editing Glossary  702
techniques to test the functioning of the snake ZRS 681 Index  725
List of Boxes
Special Interest Boxes Box 7B The cytoskeleton, cell-shape change, and cell
Box 1A Basic stages of Xenopus laevis development 4 movement278
Box 3F Identical twins 137 Box 7D Eph receptors and their ephrin ligands 313
Box 4F A zebrafish gene regulatory network 176 Box 8B Epigenetic control of gene expression by chromatin
Box 5E The Hox genes 214 modification344
Box 6C Gene silencing by microRNAs 250 Box 10C Sonic hedgehog signaling and the
Box 7C Convergent extension 302 primary cilium 466
Box 8A Conrad Waddington’s ‘epigenetic landscape’ provides a Box 12A The core Hippo signaling pathways in Drosophila and
framework for thinking about how cells differentiate 335 mammals559
Box 9A Polar bodies 405
Box 10A Positional information and morphogen gradients 443 Experimental Boxes
Box 10E Reaction–diffusion mechanisms 476 Box 1D Visualizing gene expression in embryos 20
Box 11A Specification of the sensory organs of adult Drosophila 523 Box 2A Mutagenesis and genetic screening strategy for
Box 11C The development of the neural circuit for the identifying developmental mutants in Drosophila 43
knee-jerk reflex 532 Box 2D Targeted gene expression and misexpression screening 69
Box 12B Digit length ratio is determined in the embryo 568 Box 2F Mutants in denticle pattern provided
Box 12C Regeneration in Hydra580 clues to the logic of segment patterning 81
Box 12D Planarian regeneration 582 Box 3A Gene-expression profiling by DNA microarrays and
Box 12E Why can’t we regenerate our limbs? 592 RNA seq 117
Box 13A Angiosperm embryogenesis 614 Box 3B Large-scale mutagenesis screens for recessive mutations
Box 13C The basic model for the patterning of the in zebrafish 123
Arabidopsis flower 639 Box 3C The Cre/loxP system: a strategy for making gene
Box 13D The circadian clock coordinates plant growth knock-outs in mice 127
and development 643 Box 3D The CRISPR-Cas9 genome-editing system 128
Box 14A Darwin’s finches 654 Box 4D Investigating receptor function using dominant-negative
Box 14B The metazoan family tree 658 proteins159
Box 14E Origins of morphological diversity in dogs 689 Box 6B Gene silencing by antisense RNA and RNA interference 241
Box 14F Long- and short-germ development in insects 693 Box 6D The gene regulatory network for sea urchin
endomesoderm specification 265
Cell Biology Boxes Box 8C Single-cell analysis of cell-fate decisions 358
Box 1B The mitotic cell cycle 7 Box 8E The derivation and culture of mouse embryonic
Box 1C Germ layers 15 stem cells 374
Box 1E Signal transduction and intracellular signaling pathways 26 Box 8F Induced pluripotent stem cells 382
Box 2B The Toll signaling pathway: a multifunctional pathway 54 Box 8G Stem cells can be cultured in vitro to produce
Box 2C The JAK–STAT signaling pathway 58 ‘organoids’—structures that mimic tissues and organs 386
Box 2E The Hedgehog signaling pathway 80 Box 11B Timing the birth of cortical neurons 526
Box 4A Intercellular protein signals in vertebrate development 145 Box 13B Plant transformation and genome editing 620
Box 4B The Wnt/β-catenin signaling pathway 146 Box 14C Using CRISPR-Cas9 genome-editing techniques to
Box 4C Signaling by members of the TGF-β family of test the functioning of the snake ZRS 681
growth factors 155 Box 14D Pelvic reduction in sticklebacks is based on mutations
Box 4E The fibroblast growth factor signaling pathway 163 in a gene control region 686
Box 5A Fine-tuning Nodal signaling 193
Box 5B Chromatin-remodeling complexes 201 Medical Boxes
Box 5C Retinoic acid: a small-molecule intercellular signal 206 Box 1F When development goes awry 28
Box 5D The Notch signaling pathway 211 Box 3E Preimplantation genetic diagnosis 134
Box 6A Apoptotic pathways in nematodes, Drosophila, Box 7E Neural tube defects 314
and mammals 238 Box 8D Treatment of junctional epidermolysis bullosa
Box 7A Cell-adhesion molecules and cell junctions 274 with skin grown from genetically corrected stem cells 366
xxiv Contents

Box 10B Too many fingers: mutations that affect Box 10F What developmental biology can teach
antero-posterior patterning can cause polydactyly 465 us about breast cancer 486
Box 10D Teratogens and the consequences of Box 11D Autism: a developmental disorder that
damage to the developing embryo 470 involves synapse dysfunction 543
Reviewer acknowledgments

We would like to reiterate our thanks to the people who contributed to the first
five editions. Many people gave their advice based on the fifth edition, and others
reviewed the draft chapters for the sixth edition as they emerged. We wish to express
our gratitude to the following colleagues.

Katie Abley, University of Cambridge

Mike Akam, University of Cambridge
Willy M. Baarends, University Medical Centre, Rotterdam
Hegias Mira Bontenbal, University Medical Centre, Rotterdam
Thomas Butts, University of Liverpool
Sinéad Drea, University of Leicester
Sander van den Driesche, University of Edinburgh
Anna-Pavlina Haramis, Leiden University
Brigitte Galliot, University of Geneva
Erik Griffin, Dartmouth College
Jane Kenney-Hunt, Westminster College, Fulton, Missouri
Jane Langdale, University of Oxford
Tony Perry, University of Bath
Mary Elizabeth Pownall, University of York
Aida Rajic, University of Suffolk
Joanna Richardson, University of Sussex
Guojun Sheng, Kumamoto University
Kate Storey, University of Dundee
Shahragim Tajbakhsh, Institut Pasteur, Paris
Michael Taylor, Cardiff University
Adri Thomas, Utrecht University
Fiona Wardle, King’s College London
Deneen Wellik, University of Michigan Medical School,
Ann Arbor
Larissa Williams, Bates College, Lewiston, Maine

We would also like to thank our colleagues who wrote the online Journal Clubs to
accompany this edition.

Katie Abley, University of Cambridge

Zoe Burke, University of Bath
Andrew Economou, The Francis Crick Institute
Caitlin McQueen, University of Sheffield
Adriana Amorim Torres, AAT Assessoria Cientìfica
 1
History and basic concepts
● The origins of ● A conceptual tool kit
developmental biology

The aim of this chapter is to provide a conceptual framework for the study of develop-
ment. We start with a brief history of the study of embryonic development, which illus-
trates how some of the key questions in developmental biology were first formulated,
and continue with some of the essential principles of development. The big question
is: How does a single cell—the fertilized egg—give rise to a multicellular organism, in
which a multiplicity of different cell types are organized into tissues and organs to
make up a three-dimensional body? This question can be studied from many different
viewpoints, all of which have to be fitted together to obtain a complete picture of de-
velopment: which genes are expressed, and when and where; how cells communicate
with each other; how a cell’s developmental fate is determined; how cells proliferate
and differentiate into specialized cell types; and how major changes in body shape
are produced. All the information for embryonic development is contained within the
fertilized egg. We shall see that an organism’s development is ultimately driven by
the regulated expression of its genes in space and time, determining which proteins
are present in which cells and when. In turn, proteins largely determine how a cell
behaves. The genes provide a generative program for development, not a blueprint,
as their actions are translated into developmental outcomes through cellular behavior
such as intercellular signaling, cell proliferation, cell differentiation, and cell movement.

The development of a multicellular organism from a single cell—the fertilized egg—is

a brilliant triumph of evolution. The fertilized egg divides to give rise to many mil-
lions of cells, which form structures as complex and varied as eyes, arms, heart, and
brain. This amazing achievement raises a multitude of questions. How do the cells
arising from division of the fertilized egg become different from each other? How do
they become organized into structures such as limbs and brains? What controls the
behavior of individual cells so that such highly organized patterns emerge? How are
the organizing principles of development embedded within the egg, and, in particular,
within the genetic material, DNA? Much of the excitement in developmental biology
today comes from our growing understanding of how genes direct these developmen-
tal processes, and genetic control is one of the main themes of this book. Thousands
of genes are involved in controlling development, but we will focus only on those that
have key roles, and illustrate general principles.
2 Chapter 1 History and basic concepts
a Understanding how embryos develop is a huge intellectual challenge, and one of the
b ity to divide indefinitely, and so the study of embryonic cells and their behaviour could
Fig. 1.1 Human fertilized egg and embryo.
(a) Human fertilized egg. The nuclear
membranes of the sperm and egg nuclei
(pronuclei) have not yet broken down to allow
the parental chromosomes to mingle. (b) Human
embryo at around 51 days’ gestation (Carnegie
stage 20), which is equivalent to a mouse
embryo at 13.5 days post-fertilization. A human
embryo at this stage is about 21–23 mm long.
(a) Courtesy of A. Doshi, CRGH, London.
(b) Reproduced courtesy of the MRC/
Wellcome-funded Human Developmental
Biology Resource.
Fig. 1.2 The South African claw-toed frog,
Xenopus laevis. Scale bar = 1 cm.
Photograph courtesy of J. Smith.
ultimate aims of the science of developmental biology is to understand how we humans
develop (Fig. 1.1). We need to understand human development for several reasons. We
need to properly understand why it sometimes goes wrong and why a fetus may fail to
be born or a baby be born with congenital abnormalities. The link here with genetic con-
trol of development is very close, as mutations in genes can lead to abnormal develop-
ment; environmental factors, such as drugs and infections, can affect it too. Another area
of medical research related to developmental biology is regenerative medicine—finding
out how to use cells to repair damaged tissues and organs. The focus of regenerative
medicine is currently on stem cells. Stem cells that can proliferate and give rise to all
the different tissues of the body are present in embryos. These, and the stem cells with
more limited developmental potential that are found in adult tissues, are discussed in
Chapter 8. Cancer cells also display some properties of embryonic cells, such as the abil-
lead to new and better treatments for cancer, as many of the same genes are involved.
The development of an embryo from the fertilized egg is known as embryogenesis.
One of the first tasks that cells have in an embryo is to lay down the overall body plan
of the organism, and we shall see that different organisms solve this fundamental
problem in several ways. The focus of this book is mainly on animal development, in
particular that of vertebrates—frogs, birds, fish, and mammals—whose early develop-
ment is discussed in Chapters 3–5. We also look at selected invertebrates, particularly
the fruit fly and the nematode worm, and also the sea urchin. Our understanding of
the genetic control of development is founded on work with fruit flies and nematodes,
where it is also most advanced, and the main features of their early development are
considered in Chapters 2 and 6, respectively. The fruit fly is also used throughout the
book to illustrate particular aspects of development. In Chapter 13 we look briefly at
some aspects of plant development, which differs in many respects from that of ani-
mals but involves similar basic principles.
Morphogenesis, or the development of form, is discussed in Chapter 7. In Chapter
9 we look at how sex is determined and how germ cells develop. The differentiation of
unspecialized cells into cells that carry out particular functions, such as muscle cells
and blood cells, is considered in Chapter 8. Structures such as the vertebrate limb, and
organs such as insect and vertebrate eyes, the heart and the nervous system, illustrate
the problems of multicellular organization and tissue differentiation in embryogen-
esis, and we consider some of these systems in detail in Chapters 10 and 11. The study
of developmental biology, however, goes well beyond the development of the embryo.
Post-embryonic growth and aging, how some animals undergo metamorphosis, and
how animals can regenerate lost organs is discussed in Chapter 12. Taking a longer
view, we shall consider in Chapter 14 how developmental mechanisms have evolved
and how they constrain the very process of evolution itself.
One might ask whether it is necessary to cover so many different organisms in order
to understand the basic features of development. The answer is yes. Developmental
biologists do, indeed, believe that there are general principles of development that
apply to all animals, but life is too wonderfully diverse to find all the answers in a sin-
gle organism. As it is, developmental biologists have tended to focus their efforts on a
relatively small number of animals, chosen because they were convenient to study and
amenable to experimental manipulation or genetic analysis. This is why some crea-
tures, such as the frog Xenopus laevis (Fig. 1.2) and the fruit fly Drosophila melano-
gaster, have such a dominant place in developmental biology. Similarly, work with the
thale cress, Arabidopsis thaliana, has uncovered many features of plant development.
One of the most exciting and satisfying aspects of developmental biology is that
understanding a developmental process in one organism can help to illuminate sim-
ilar processes elsewhere—for example, giving insights into how humans develop.
Nothing illustrates this more dramatically than the influence that our understanding
of Drosophila development, and especially of its genetic basis, has had throughout
Another random document with
no related content on Scribd:
expenses, including legal fees. YOU AGREE THAT YOU HAVE NO
REMEDIES FOR NEGLIGENCE, STRICT LIABILITY, BREACH OF
WARRANTY OR BREACH OF CONTRACT EXCEPT THOSE
PROVIDED IN PARAGRAPH 1.F.3. YOU AGREE THAT THE
FOUNDATION, THE TRADEMARK OWNER, AND ANY
DISTRIBUTOR UNDER THIS AGREEMENT WILL NOT BE LIABLE
TO YOU FOR ACTUAL, DIRECT, INDIRECT, CONSEQUENTIAL,
PUNITIVE OR INCIDENTAL DAMAGES EVEN IF YOU GIVE
NOTICE OF THE POSSIBILITY OF SUCH DAMAGE.

1.F.3. LIMITED RIGHT OF REPLACEMENT OR REFUND - If you

discover a defect in this electronic work within 90 days of receiving it,
you can receive a refund of the money (if any) you paid for it by
sending a written explanation to the person you received the work
from. If you received the work on a physical medium, you must
return the medium with your written explanation. The person or entity
that provided you with the defective work may elect to provide a
replacement copy in lieu of a refund. If you received the work
electronically, the person or entity providing it to you may choose to
give you a second opportunity to receive the work electronically in
lieu of a refund. If the second copy is also defective, you may
demand a refund in writing without further opportunities to fix the
problem.

1.F.4. Except for the limited right of replacement or refund set forth in
paragraph 1.F.3, this work is provided to you ‘AS-IS’, WITH NO
OTHER WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED,
INCLUDING BUT NOT LIMITED TO WARRANTIES OF
MERCHANTABILITY OR FITNESS FOR ANY PURPOSE.

1.F.5. Some states do not allow disclaimers of certain implied

warranties or the exclusion or limitation of certain types of damages.
If any disclaimer or limitation set forth in this agreement violates the
law of the state applicable to this agreement, the agreement shall be
interpreted to make the maximum disclaimer or limitation permitted
by the applicable state law. The invalidity or unenforceability of any
provision of this agreement shall not void the remaining provisions.
1.F.6. INDEMNITY - You agree to indemnify and hold the
Foundation, the trademark owner, any agent or employee of the
Foundation, anyone providing copies of Project Gutenberg™
electronic works in accordance with this agreement, and any
volunteers associated with the production, promotion and distribution
of Project Gutenberg™ electronic works, harmless from all liability,
costs and expenses, including legal fees, that arise directly or
indirectly from any of the following which you do or cause to occur:
(a) distribution of this or any Project Gutenberg™ work, (b)
alteration, modification, or additions or deletions to any Project
Gutenberg™ work, and (c) any Defect you cause.

Section 2. Information about the Mission of

Project Gutenberg™
Project Gutenberg™ is synonymous with the free distribution of
electronic works in formats readable by the widest variety of
computers including obsolete, old, middle-aged and new computers.
It exists because of the efforts of hundreds of volunteers and
donations from people in all walks of life.

Volunteers and financial support to provide volunteers with the

assistance they need are critical to reaching Project Gutenberg™’s
goals and ensuring that the Project Gutenberg™ collection will
remain freely available for generations to come. In 2001, the Project
Gutenberg Literary Archive Foundation was created to provide a
secure and permanent future for Project Gutenberg™ and future
generations. To learn more about the Project Gutenberg Literary
Archive Foundation and how your efforts and donations can help,
see Sections 3 and 4 and the Foundation information page at
www.gutenberg.org.

Section 3. Information about the Project

Gutenberg Literary Archive Foundation
The Project Gutenberg Literary Archive Foundation is a non-profit
501(c)(3) educational corporation organized under the laws of the
state of Mississippi and granted tax exempt status by the Internal
Revenue Service. The Foundation’s EIN or federal tax identification
number is 64-6221541. Contributions to the Project Gutenberg
Literary Archive Foundation are tax deductible to the full extent
permitted by U.S. federal laws and your state’s laws.

The Foundation’s business office is located at 809 North 1500 West,

Salt Lake City, UT 84116, (801) 596-1887. Email contact links and up
to date contact information can be found at the Foundation’s website
and official page at www.gutenberg.org/contact

Section 4. Information about Donations to

the Project Gutenberg Literary Archive
Foundation
Project Gutenberg™ depends upon and cannot survive without
widespread public support and donations to carry out its mission of
increasing the number of public domain and licensed works that can
be freely distributed in machine-readable form accessible by the
widest array of equipment including outdated equipment. Many small
donations ($1 to $5,000) are particularly important to maintaining tax
exempt status with the IRS.

The Foundation is committed to complying with the laws regulating

charities and charitable donations in all 50 states of the United
States. Compliance requirements are not uniform and it takes a
considerable effort, much paperwork and many fees to meet and
keep up with these requirements. We do not solicit donations in
locations where we have not received written confirmation of
compliance. To SEND DONATIONS or determine the status of
compliance for any particular state visit www.gutenberg.org/donate.

While we cannot and do not solicit contributions from states where

we have not met the solicitation requirements, we know of no
prohibition against accepting unsolicited donations from donors in
such states who approach us with offers to donate.

International donations are gratefully accepted, but we cannot make

any statements concerning tax treatment of donations received from
outside the United States. U.S. laws alone swamp our small staff.

Please check the Project Gutenberg web pages for current donation
methods and addresses. Donations are accepted in a number of
other ways including checks, online payments and credit card
donations. To donate, please visit: www.gutenberg.org/donate.

Section 5. General Information About Project

Gutenberg™ electronic works
Professor Michael S. Hart was the originator of the Project
Gutenberg™ concept of a library of electronic works that could be
freely shared with anyone. For forty years, he produced and
distributed Project Gutenberg™ eBooks with only a loose network of
volunteer support.

Project Gutenberg™ eBooks are often created from several printed

editions, all of which are confirmed as not protected by copyright in
the U.S. unless a copyright notice is included. Thus, we do not
necessarily keep eBooks in compliance with any particular paper
edition.

Most people start at our website which has the main PG search
facility: www.gutenberg.org.

This website includes information about Project Gutenberg™,

including how to make donations to the Project Gutenberg Literary
Archive Foundation, how to help produce our new eBooks, and how
to subscribe to our email newsletter to hear about new eBooks.