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 Atlas of Early Zebrafish
Brain Development
A Tool for Molecular Neurogenetics
Atlas of Early Zebrafish
Brain Development
A Tool for Molecular Neurogenetics

Thomas Mueller
Kansas State University
Manhattan, KS, United States of America

Mario F. Wullimann
Ludwig-Maximilians-Universität Munich
Munich, Germany

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ISBN: 978-0-12-418669-9

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Preface 2015

So, here we are again 10 years down the road. Meanwhile, the zebraf-
ish field has remarkably progressed. The first edition of our atlas promoted new
and effective ways of identifying expression patterns in the early zebrafish brain.
Clearly, standards for neuroanatomical studies in zebrafish have increased. For
example, there is a marked increase in zebrafish-related papers in the Journal of
Comparative Neurology if we compare the years prior to the publication of our atlas
(1994-2004) to the decade after its publication (2004-2014). A quick PubMed search
in these two decades reveals a doubling of hits, that is, 54 versus 118 papers. In
similar ways, we find a significant increase in the application of large-scale and
3D confocal imaging technique often using transgenic lines. Still, only precise
identification of zebrafish brain structures in a comparative context will allow
­integration of data from the fields of molecular neuroanatomy, transcriptome, and
connectome studies.
To provide maximal consistency with the first edition, we kept the struc-
ture of Chapter 1 (historical account) and Chapter 2 (atlas). Notably, we added
a number of new plates of immunofluorescence microphotographs to illustrate
GABA cell development. In contrast, we greatly modified design and content of
Chapters 3 and 4. Chapter 3 now offers a more comprehensive analysis of the
development of all major transmitter phenotypes, and in particular glutamatergic
and GABAergic neurons. In addition, we describe critical modulatory transmitter
systems, such as the dopaminergic, noradrenergic, serotoninergic, histaminergic,
and cholinergic neurons. We also comment on glycinergic neurons, and we fo-
cus on the two regions with unusual nonperiventricular proliferation in the dien-
cephalon and the cerebellum. Finally, we compare various BrdU approaches and
­discuss their usefulness for developmental fate studies.
Chapter 4 provides a broad comparative overview. It explains how
­zebrafish data on neurogenesis are embedded in the vertebrate evo-devo context,
in particular in relation to data from the mouse and frog (Xenopus). This chapter
also contrasts conserved developmental processes in various vertebrate model
systems with ontogenetic peculiarities of zebrafish.

ix
 Preface 2015 

The second edition of the Atlas, thus, offers a more complete and balanced
view of neurogenetic events in the zebrafish brain. We also advance a comparative
evaluation of these events in the context of key model animals. We hope that this
second edition will again be well received in the zebrafish community.

Thomas Mueller
Mario F. Wullimann
Manhattan (Kansas, United States of America)
and Martinsried (Germany)—Spring 2015

x
Preface 2005

No one doubts that methodological revolutions shape the direction of

­science. For instance, the invention of the microscope led almost directly to the
recognition of the cell as the basic module of all organisms. Equally decisive for the
scientific progress are ideas and concepts, which sometimes predate their confir-
mation by adequate methodology. These two closely intertwined processes shape
past and present scientific endeavors and are part of human culture created by the
efforts of people interconnected by a common interest in similar questions over
many decades. The admiration for methodological innovations and the respect for
scientific ideas or concepts both represent important foundations of science.
Therefore, the first chapter of this book puts into perspective historically
important contributions to the field of early vertebrate central nervous system
development. With this, we wish to clarify how the cellular–molecular data de-
livered in the second, main chapter relate to the larger neurobiological context of
neurogenesis in early brain development. The second chapter delivers the actual
atlas pages that the readership may use pragmatically to identify certain early
zebrafish brain areas. The third chapter takes up the dynamic aspects of how the
atlas may be used, be it to elucidate locally differing dynamics of proliferation,
determination, and differentiation of neural cells or to implement additional gene
expression data. Finally, the fourth chapter delivers a comparative perspective
of gene expression patterns between major model animals, especially between
mouse and zebrafish.
In addition to delivering a refined early neuroanatomy of the zebrafish
brain, the cellular and molecular genetic nature of the data presented in this book
allows a starting point for understanding the local differences in the distribution
of proliferative, early neuronally determined and differentiating cells and their
underlying neurogenetic pathways. The book also is intended to facilitate the use
of the zebrafish model animal in many future neurobiologically oriented investi-
gations in basic as well as biomedically relevant research projects.

xi
Acknowledgments

One of the pleasures of finishing a book is to acknowledge the colleagues

and friends who gave important feedback, supplied us with probes, and s­ upported
the project in various ways. Thanks go to Patrick Blader (Toulouse, France);
Uwe Strähle (Karlsruhe, Germany); Michael Lardelli (Adelaide, Australia); Eric
Weinberg (Philadelphia, PA, USA); and Rachel McDonald, Ingvild Mikkola, and
Steve Wilson (London, UK) for providing probes and antibodies. A big merci
goes to Philippe Vernier (Gif-sur-Yvette, France) for enabling us to embark on
this ­project in the first place. Thomas Mueller also thanks Wolfgang Driever
(University of Freiburg, Germany) for his support above and beyond what can
be expected. In addition, Thomas Mueller is grateful for the generous support
of Brian Spooner, Susan Brown, and Gary Conrad from the Division of Biology
at Kansas State University. Mario Wullimann thanks Benedikt Grothe (Ludwig-
Maximilians-Universität Munich, Germany) for continuing support. Last but not
least, this second edition would not have been possible without support and un-
derstanding of our families and friends. Thomas Mueller thanks Steffi Dippold;
without her presence, work on this book would not have been half as enjoyable.

xiii
 Vertebrate Central Nervous System
Development

Chapter 1
Introduction
Atlas of Early Zebrafish Brain Development. http://dx.doi.org/10.1016/B978-0-12-418669-9.00001-5
© 2016 Elsevier B.V. All rights reserved.
 1. Vertebrate Central Nervous System Development

1. Vertebrate Central Nervous System Development

1.1 Introductory Remarks: The Order of the Universe

The individual universe each human being mentally carries around is a

product of our brain, which most likely represents the most complex object in the
world. How does the brain come into existence during development? The ontog-
eny of the vertebrate central nervous system (CNS: brain and spinal cord) itself is
a highly complex yet strongly conserved morphogenetic process. The early ver-
tebrate embryo exhibits three embryonic cellular sheets called germ layers, the
most peripheral one being the ectoderm. Its dorsal portion represents the neuro-
ectoderm that develops into the prospective nervous system. The neuroectoderm
segregates early from the ventrolaterally lying general ectoderm, which forms the
future epidermal skin and its derivatives. Subsequently, the central main portion
of the neuroectoderm, the neural plate, is “swallowed” by the general ectoderm
through the process of neurulation. As a result, the neural plate separates from
the general ectoderm and descends into the deep of the embryo, where it devel-
ops into a hollow neural tube surrounding a cerebrospinal fluid- (liquor-) filled
ventricle. Meanwhile, the general ectoderm closes the temporarily opened dorsal
backside of the embryo. The apparent formation along the anteroposterior axis of
initially three brain vesicles (forebrain, midbrain, hindbrain) that transform sub-
sequently into five brain vesicles (telencephalon, diencephalon, mesencephalon,
metencephalon, myelencephalon) somewhat hides the parallel establishment of
finer transverse subdivisions called neuromeres (rhombomeres in the hindbrain,
prosomeres in the forebrain, see later). What follows is the differentiation of func-
tional subdivisions of the brain and spinal cord (for example, the optic tectum/
superior colliculus, a midbrain sensorimotor integration center, or the hypothala-
mus, the major control center of visceral processes).
These events of vertebrate CNS formation are accompanied by the em-
igration of the most lateral portions of the neuroectoderm, the neural folds
(Neuralwülste) and some directly adjacent neuroectodermal regions, which are
not incorporated into the neural tube during neurulation. These neuroectodermal
components comprise the neural crest of the head and trunk and the placodes that
are located in the head only. Eventually neural crest and placodes give rise to cells
that migrate to their final destination in the adult body, where they form almost all
sensory organs and the sensory neurons in dorsal root and cranial nerve ganglia,

3
 1. Vertebrate Central Nervous System Development

which innervate them, and the visceral ganglia of the autonomic nervous system.
These somatic and visceral ganglia and their associated nerves represent the pe-
ripheral nervous system (PNS).
For many decades, scientists have investigated these complex develop-
mental events leading to the formation of a nervous system in various vertebrates,
especially in model animals, such as in the African clawed frog Xenopus, the chick,
rodents like the mouse and rat, and most recently, the zebrafish, at molecular, cel-
lular, histological, or morphological levels. Thus, a wealth of scientific literature is
available, ready to satisfy almost any hunger for information.
Why then the present book? First of all, it integrates knowledge on CNS
development coming from classical developmental studies with recent molec-
ular data related to neuro- and gliogenesis. In particular, we will demonstrate
the detailed spatiotemporal order of early postembryonic zebrafish brain de-
velopment using molecular and cellular markers of neuro- and gliogenesis to
visualize local differences, embedded in a holistic morphogenetic context. By
combining old and new knowledge, we provide a neuroanatomically based mo-
lecular atlas of neural development in the zebrafish brain. We hope that such
information—beyond delivering a refined molecular neuroanatomy—will prove
to be enlightening in the future elucidation of neurogenetic pathways and their
mechanisms.

1.2 Major Developmental Stages of the Vertebrate Neural Tube

Historically, scientists have always aimed to identify the fundamental

building blocks of the vertebrate brain. In other words, they have tried to de-
termine the basic developmental brain units and to answer the question of how
these transform into functional structures of the mature brain. Before going into
a more detailed discourse of the development of finer brain subdivisions (see
Section 1.3), we will shortly examine the early events of brain morphogenesis
relating to the emergence of vesicles and neuromeres, as well as of longitudinal
zones, followed by an account on the neuromeric (prosomeric) model and on
central nervous neurogenesis. An excellent in-depth historical account on the un-
derstanding of vertebrate brain morphogenesis has been given by Nieuwenhuys
(1998a,b,c).

4
 1. Vertebrate Central Nervous System Development

1.2.1 Vesicles, Neuromeres, and Longitudinal Zones

The classical description of a sequential appearance of two, three, and

then five brain vesicles (i.e., transverse elements) along the anteroposterior verte-
brate neural tube axis dates back to von Baer (1828). This view, however, gained
popularity in the early twentieth century with the works of von Kupffer (1906)
and Johnston (1909). The two-vesicle stage comprises a combined forebrain (pros-
encephalon) and midbrain (mesencephalon) vesicle, which is set apart by a verti-
cal neural tube constriction from the hindbrain (rhombencephalon) vesicle. This is
followed by the three-vesicle stage displaying forebrain, midbrain, and hindbrain
vesicles (see Fig. 1) and, finally, by the five-vesicle stage, consisting of telenceph-
alon and diencephalon (together forming the forebrain), mesencephalon, as well
as metencephalon and myelencephalon (together forming the rhombencephalon).

Fig. 1. Schematic lateral view of early mouse brain (E 12.5-13.5) shows prosomeric interpretation
(Puelles and Rubenstein, 1993, 2003), including transverse (neuromeres) and longitudinal (columns)
elements. Arrows designate anteroposterior axis of neural tube. Abbreviations: AP: alar plate; BP:
basal plate; DT: dorsal thalamus (thalamus), FP: floor plate; P1-P3: prosomeres 1-3 (for more details
see text); Pr: pretectum; Rh1-Rh8: rhombomeres 1-8; RP: roof plate; sm: somatomotor column; ss:
somaotosensory column; T: telencephalon; vm: visceromotor column; vs: viscerosensory column;
VT: ventral thalamus (prethalamus).

The subdivision of both forebrain and hindbrain into two separable (trans-
verse) vesicles, each along the anteroposterior axis, arguably is an epiphenome-
non, visible only in mammalian embryos that show an enormous early growth of
the telencephalic hemispheres. This hypertrophy detracts from the fact that the

5
 1. Vertebrate Central Nervous System Development

most rostral vertebrate neural tube in reality includes in addition to the dorsally
lying telencephalon also ventrally the smaller hypothalamus. This renders the
concept of transverse telencephalic and diencephalic vesicles obsolete because
part of the diencephalon (the hypothalamus) is included in a transverse unit with
the telencephalon (Puelles and Rubenstein, 1993, 2003). Also, the somewhat later,
characteristic mammalian emergence of a large cerebellum and ventral pontine
region led to the impression that the medulla oblongata develops from two sepa-
rable vesicles, the metencephalic one exhibiting cerebellum and pons, and a my-
elencephalic vesicle posteriorly. Indeed, the dorsal portion of the anteriormost
rhombomere specializes into a dorsal cerebellum. In contrast, the ventral pontine
region, which relays cortical information to the cerebellum, develops from ventral
and fused portions of rhombomeres 1-4 (Aroca and Puelles, 2005; Alonso et al.,
2012). This complex development of the anterior hindbrain historically resulted
in the misinterpretation that the two enlargements of cerebellum and pons form a
true transverse unit, which was called the metencephalon to separate it from the
posterior myelencephalon. However, the medulla oblongata does not show a real
boundary between these two postulated vesicles; instead, it is rather divided into
a higher number of early segmental entities, the rhombomeres (see later discus-
sion and Fig. 1).
In contrast, the three-vesicle stage reflects on fundamental anteroposterior
vertebrate brain divisions. Especially the midbrain-hindbrain boundary has been
strongly corroborated in modern developmental neurobiology as a singularly de-
finable boundary and signaling center in the vertebrate brain (Marín and Puelles,
1994; Bally-Cuif and Wassef, 1995; Brand et al., 1996; Lumsden and Krumlauf,
1996; Reifers et al., 1998; Wurst and Bally-Cuif, 2001). Similarly, there is clear evi-
dence for cellular lineage restriction (Larsen et al., 2001) and signaling center func-
tion (Scholpp and Brand, 2003) at the forebrain-midbrain boundary.
Equally important for the understanding of the vertebrate CNS bauplan
are two neural tube flexures, which were also historically noted early (His, 1888,
1893a). The cephalic flexure of the anteroposterior axis is between the mesen-
cephalon and the prosencephalon, and the cervical flexure is between the rhomb-
encephalon and the spinal cord (compare Fig. 1). The result of this bending of
the neuraxis is that the forebrain floor is adjacent to the hindbrain floor. The cor-
rect recognition of the adequate course of the anteroposterior axis of the neural
tube has important consequences for the interpretation of the topology of brain
structures.

6
 1. Vertebrate Central Nervous System Development

Whereas the vesicle story just outlined found its way easily into general
textbook knowledge, the historical equally early description of neural tube seg-
ments or so-called neuromeres did not. Neuromeres represent a finer set of tran-
sitory transverse or segmental divisions of the vertebrate neural tube, and they
remain, at least partially, controversial to the present day. Vertebrate hindbrain
neuromeres (rhombomeres) are set apart from each other by transverse, vertical
constrictions and were already described in the nineteenth century (von Baer,
1828; Orr, 1887). Later, similar morphological observations led to the interpreta-
tion of neuromeres to extend into midbrain (mesomeres) and forebrain as well
(prosomeres; see Fig. 1; Rendahl, 1924; Bergquist, 1932; Vaage, 1969). However,
in these early twentieth-century studies, the basis for recognizing transverse neu-
romeres was descriptive (and, even worse, transitory) morphology. Thus, seri-
ous opposition regarding the acceptance of neuromeres as the important building
blocks of the CNS arose with its growing functional neuroanatomical understand-
ing, especially by the so-called American school, which was based on the early
work of Gaskell (1889) and later widely spread through the activities of Charles
Judson Herrick (1868-1960), who is viewed as one of the founding fathers of mod-
ern comparative neurology. In this school's well corroborated view, longitudinal
functional zones—embryonically represented dorsoventrally in the neural tube
as roof, alar, basal, and floor plates (His, 1888, 1893a,b)—were considered the pri-
mary subdivisions of the CNS (see Fig. 1). Both the most dorsal (roof plate) and
most ventral (floor plate) longitudinal zones exert critical developmental roles,
for example, in mediating dorsoventral polarity of the neural tube or in guid-
ing neuronal differentiation processes. In the adult vertebrate CNS, the roof plate
gives rise to dorsal midline structures, such as the epiphysis or the choroid plexus,
which covers the rhomboid opening of the medulla oblongata, whereas the floor
plate develops, for example, into ventral midline glial cells.
The two intermediate longitudinal zones termed the alar and basal plates
form pivotal elements of Herrick's concept of functional vertebrate brain and spi-
nal cord organization. Alar and basal plate derivatives form the characteristic dor-
soventral arrangement of four functional longitudinal subzones, that is, alar plate
derived somato- and viscerosensory columns and basal plate derived viscero- and
somatomotor columns as prototypically present in the spinal cord (see Fig. 1).
This dorsoventral spinal cord organization of four sensory and motor zones has
been used to consistently explain various local specializations (hypertrophies and
reductions) in more anterior brain regions—at least into the midbrain. Thus, this

7
 1. Vertebrate Central Nervous System Development

concept of longitudinal functional zones understandably gained much accep-

tance, and it is still discussed in recent textbooks.
A related question is how far anteriorly the vertebrate brain longitudinal
zones extend (see Nieuwenhuys, 1998a). Considering alar and basal plates, there
were two factions. Kingsbury (1922) believed that the basal plate tapers out at
the mesencephalic-diencephalic boundary and that the alar plate alone forms the
more anterior brain parts. Similarly, Herrick (1910) had proposed that the basal
plate becomes thinner anteriorly and yet would only continue into the hypo-
thalamus. Here, Herrick's original sin comes in: He believed that the more dor-
sal diencephalic divisions (ventral thalamus, dorsal thalamus, and epithalamus)
all represent longitudinal zones (functionally elaborated alar plate subdivisions
that he even saw to continue into the telencephalon), which turned out to be a
false concept with long-lasting consequences (see later discussion). Kuhlenbeck
(publications between 1926 and 1973; see Nieuwenhuys, 1998a) was supportive of
Herrick's longitudinal zone concept (including the diencephalon), but highlighted
its bauplan nature, disregarding the functional aspect. In contrast, Bergquist and
Källén (1954)—similar to His (1888, 1893a,b)—proposed the continuation of both
alar and basal plates into the general region of the optic chiasm/preoptic region.
Thus, in line with their neuromeric concept, the forebrain prosomeres contained
alar and basal plate derivatives. This has the important consequence that dorsal
and ventral thalamus (and pretectum, for that matter) represent transverse—not
longitudinal—elements along the anteroposterior neural tube axis, which is a now
widely accepted concept (see Fig. 1 and following discussion).
Starting in the 1980s, vertebrate brain neuromery has been reconsidered
and confirmed. However, a deep schisma exists between today's “segmentalists.”
Mostly dealing with rhombomeres (Hannemann et al., 1988; Holland and Hogan,
1988; Keynes and Stern, 1988; Lumsden and Keynes, 1989; Murphy et al., 1989;
Lumsden, 1990; Trevarrow et al., 1990; Wilkinson and Krumlauf, 1990; Clarke and
Lumsden, 1993; Lumsden and Krumlauf, 1996), many recent researchers stress
that rigorous criteria for real transverse (neuromeric) neural tube elements (i.e.,
containing a piece of roof, alar, basal, and floor plates each) are exclusively met by
rhombomeres. Among those criteria are glial intersegmental boundaries, repeti-
tive (metameric) segmental generation of comparable neuronal classes and axonal
routing in each neuromere, and most important, neuromere-specific cellular lin-
eage restriction (Fraser et al., 1990). These criteria led to the most stringent defi-
nition available of a segment or neuromere as constituting a neural compartment

8
 1. Vertebrate Central Nervous System Development

(Larsen et al., 2001). Strong complementary supporting evidence from molecular

genetic studies showed that various regulatory genes, especially those of the Hox
B cluster (Graham et al., 1989; Hunt and Krumlauf, 1992) or other genes, such
as Krox20 (Wilkinson et al., 1989a,b; Oxtoby and Jowett, 1993) are hierarchically
or specifically expressed respecting rhombomere boundaries, thereby confining
positional information to the rhombomeres. Rhombomeric development finally
leads to the different adult phenotypical identities of their respective derivatives
along the anteroposterior hindbrain axis.
Also forebrain neuromeres have been rediscovered in vertebrates re-
cently, and various numbers of such prosomeres were proposed based on new
data (Puelles et al., 1987; Figdor and Stern, 1993; Puelles and Rubenstein, 1993,
2003). The most prominent contemporary, the so-called neuromeric or prosomeric
model by Puelles and Rubenstein (1993, 2003) suggests an overall segmentation
of the vertebrate brain and we will discuss this model in some more detail later.
Generally, it may be stated that prosomeres (compare with Fig. 1) have not been
corroborated equally well using the criteria applied to rhombomeres. However,
cellular lineage restriction occurs at the forebrain-midbrain boundary, specifically
between pretectum (synencephalon; P1) and mesencephalon (Larsen et al., 2001),
and between dorsal and ventral thalamus mediated by the zona limitans intrath-
alamica (Zeltser et al., 2001). The zona limitans intrathalamica represents a transi-
tory transitional region between dorsal and ventral thalamus, thereby separating
and characterizing P2 (posterior parencephalon) and P3 (anterior parencephalon
or prethalamus) as neuromeres. The diencephalon has alternatively been reported
to contain four neuromeres (Figdor and Stern, 1993) characterized by lineage re-
striction, that is, two for the synencephalon (P1), and one each for the dorsal (P2)
and ventral thalami (P3). Additional potential prosomere boundaries, especially
those anterior to P3 (i.e., in the secondary prosencephalon) remain largely unex-
plored in the context of cellular lineage restriction.
Furthermore, as in the rhombencephalon, some early active regulatory
genes are expressed in specific prosomeres (e.g., Prox in P1, Gbx2 in P2, Dlx2 in
P3; Larsen et al., 2001) or respect at least partial prosomeric boundaries with their
expression domains (Simeone et al., 1992a; Boncinelli et al., 1993, 1995; Bulfone
et al., 1993a,b; Puelles and Rubenstein, 1993, 2003). Our own studies regarding the
distribution of early proliferation zones support the presence of three posterior
prosomeres, that is, P1 through P3 (Wullimann and Puelles, 1999; Mueller and
Wullimann, 2002b), whereas no prosomeres are recognized based on p
­ roliferation

9
 1. Vertebrate Central Nervous System Development

patterns in the more anterior forebrain (secondary prosencephalon). Also, neu-

rogenic (Notch/Delta) and proneural (basic helix-loop-helix) gene expression
closely parallels brain proliferation patterns, including the prosomeric pattern
(P1/P2/P3) in the posterior forebrain (Mueller and Wullimann, 2003; Wullimann
and Mueller, 2004a,b; see later).
In conclusion, there is strong evidence for three posterior prosomeres (P1
through P3) in the vertebrate forebrain, with the situation in the more anterior
forebrain (secondary prosencephalon) being more elusive. Clearly, rhombom-
eres match better the criteria for neuromeres/compartments when compared to
prosomeres. However, one must keep in mind that these criteria are only met
transitionally during neuromere development and that the most critical criterion,
that is, cell lineage restriction, is at no time completely met even in rhombom-
eres; there are reports on more than 5% of cells transgressing rhombomere bound-
aries (Birgbauer and Fraser, 1994). Furthermore, overt metameric organization
(i.e., similar sets of anteroposteriorly repeated classes of neurons) as seen in the
developing hindbrain does not necessarily require segmental neural tube orga-
nization during development. Metameric organization, as partially still present
in the adult rhombencephalon, is even more pervasive in the spinal cord, which
does not exhibit neuromeres (as defined earlier) during any period of develop-
ment (Keynes and Stern, 1984). Therefore, metamery is apparently not necessar-
ily strictly developmentally correlated with a neuromeric organization. Thus, the
forebrain simply may be characterized by very early individual regulation of each
of its transverse entities, resulting in a fast variable differentiation of neuromeres
and their derivatives.

1.2.2 The Neuromeric or Prosomeric Model

Irrespective of the ongoing dispute about the identification and finite

numbers of vertebrate neuromeres, Puelles and Rubenstein's neuromeric or pro-
someric model (1993, 2003) integrates and puts into perspective much of the is-
sues raised earlier, suggesting a vertebrate brain bauplan that has been of great
heuristic value in many studies since. The correct topological identification of a
particular brain structure, and, therefore, its comparative interpretation, critically
depends on the concept of the basic vertebrate CNS bauplan one uses. Such a bau-
plan involves more than the recognition of transverse elements, it also requires to
adequately indicate the course of the anteroposterior axis along the neural tube

10
 1. Vertebrate Central Nervous System Development

and, in consequence, of the longitudinal zones. Following the neuromeric model,

all central nervous longitudinal zones (floor, basal, alar, and roof plates) princi-
pally extend into the forebrain: The roof plate ends in the region of the anterior
commissure, the floor plate at the anterior end of the mammillary hypothalamus
(see two respective black dots in Fig. 1), whereas the basal and alar plate form a
broad anterior end of the neural tube with the preoptic region (alar) and hypothal-
amus (basal), both united at the area of the optic chiasma (Puelles et al., 2013). The
entire telencephalic hemispheres are thus lateral extensions of the alar plate. This
is supported by studies on various longitudinally expressed genes (such as, for
example, sonic hedgehog), which continue anteriorly to be expressed into the fore-
brain (Ericson et al., 1995; Shimamura et al., 1995, 1997; Hauptmann and Gerster,
2000). Such data clearly corroborate the old observation noted earlier that the an-
teroposterior axis of the rostral vertebrate neural tube is considerably deflected
ventrally (compare with Fig. 1). Understanding the course of longitudinal zones
is critical for the interpretation of transverse neural tube units (neuromeres), as
the latter must lie perpendicular to the anteroposterior axis. In the neuromeric
model of Puelles and Rubenstein (1993), the entire brain is principally divided
into transverse zones (each containing a segment of all longitudinal zones), and
neuromeres therefore exist not only in the rhombencephalon (rhombomeres), but
also in the mesencephalon (mesomeres) and prosencephalon (prosomeres), very
much following the ideas of Bergquist and Källén described earlier. In a revision
of their original model, Puelles and Rubenstein (2003) have modified their initial
claim of six prosomeres, suggesting only three posterior diencephalic prosomeres
(P1/P2/P3), with the secondary prosencephalon possibly guided by different pro-
cesses of regionalization, much like the conclusion reached in other recent studies
discussed earlier (e.g., Wullimann and Puelles, 1999). However, we interpret the
eminentia thalami as described here in the zebrafish as lying outside of the ventral
thalamus, because some of the revisions (Puelles and Rubenstein, 2003) are based
on information unavailable yet in the zebrafish (see also a later section: A Word
Regarding Terminology and Ontology).
Despite some insecurity about the finite number of prosomeres, it is im-
portant to accept the longitudinal axis proposed in the neuromeric model to in-
terpret adequately the topological transformation of longitudinal and transverse
elements that occurs during the development of a theoretically straight vertebrate
neural tube. A good example is the hypothalamus and the posteriorly adjacent
basal diencephalic regions (i.e., retromammillary area in P3, posterior tuberculum

11
 1. Vertebrate Central Nervous System Development

in P2, basal synencephalon in P1), which are recognized to represent basal (and
floor) plate portions of the forebrain neural tube only when this deflected axis is
respected (compare with Fig. 1). The corresponding forebrain alar (and roof) plate
complements are represented by telencephalon/preoptic region for the hypothal-
amus and by the dorsal aspects of ventral and dorsal thalami (prethalamus and
thalamus of Puelles and Rubenstein, 2003) and of pretectum for the three basal di-
encephalic regions just mentioned. A still widely accepted textbook opinion going
back to C.J. Herrick (see earlier) holds that the diencephalon (i.e., hypothalamus,
posterior tuberculum, thalamus, epithalamus, pretectum) is a transverse piece of
the neural tube in which the hypothalamus represents the most ventral (i.e., basal)
part, and the ventral thalamus, dorsal thalamus, and epithalamus are successively
more dorsal parts of the diencephalic neural tube. In contrast, the neuromeric
model considers the hypothalamus to represent the basal (ventral) part of the neu-
ral tube, associated with the dorsally located telencephalon (together representing
the anterior forebrain or secondary prosencephalon; i.e., the most rostral piece of
the neural tube). Accordingly, retromammillary region, posterior tuberculum (in
the zebrafish corresponding to ventral and dorsal posterior tuberculum, respec-
tively) and basal synencephalon represent three basal (ventral) forebrain portions
associated with the corresponding alar plate portions (i.e., ventral thalamus, dorsal
thalamus, pretectum) of the caudally adjoining piece of the neural tube (together
forming the three prosomeres that constitute the posterior forebrain, i.e., ante-
rior parencephalon, posterior parencephalon, and synencephalon). This example
shows that it is far from trivial to disclose which CNS bauplan or model one uses to
interpret the correct topological position of a particular area within the neural tube.

1.2.3 The Next Dimension: Understanding Central Nervous

Proliferation and Neuro-/Gliogenesis

Along with the emergence of an increasingly adequate picture of relevant

transverse and longitudinal elements of the vertebrate CNS, important concepts
of cellular (neural) proliferation arose through the twentieth century. In princi-
ple, the neural tube could increase its size and develop various vesicles and neu-
romeres described earlier without cell proliferation; indeed, cell shape changes
and transitory increase in liquor pressure have been implied in these processes.
However, there is now ample evidence that cell proliferation (followed by migra-
tion and differentiation) is indeed involved in the shaping of the early CNS.

12
 1. Vertebrate Central Nervous System Development

Historically, the Swedish comparative embryological school initiated

by Nils Holmgren (and continued by Palmgren, Bergquist, and Källén) plays a
crucial role in the understanding of how cellular proliferation relates to morpho-
genetic processes in the CNS, such as, for example, in the establishment of neu-
romeres. The central concept of the Swedish school is that the origin of adult brain
structures from a particular location within the proliferative periventricular sheet
of the neural tube is decisive for the final phenotypic appearance of those brain
structures and, particularly, for their comparative interpretation, that is, for iden-
tifying homologies among brain structures in different vertebrate brains. Clearly
at the core of this concept are local differences in the spatiotemporal proliferative
behavior in the periventricular neural tube sheet and the subsequent migratory
and differentiating behavior of brain cells originating there. This introduces the
third dimension necessary to understand the complexity of brain morphogene-
sis in addition to those two discussed earlier (i.e., transverse and longitudinal
neural tube elements), namely the developmental relationship of the proliferative
ventricular zones (matrix) with the more peripheral (subpial) postmitotic cellular
central nervous architecture deriving from these ventricular zones (Fig. 2).

Fig. 2. Schematic transverse view of the developing vertebrate neural tube wall emphasizing distri-
bution of proliferative, migrating, and differentiating neural cells from ventricle to pia.

Using descriptive histology, Bergquist (1932, 1954) and Källén (1951, 1952;
see also Bergquist and Källén, 1954) brought this approach to fruition and estab-
lished a grid of proliferating matrix zones (Grundgebiete) in the early vertebrate
brain. These matrix zones were described to give off neurons in a locally specific
spatiotemporal order, and—together with the subsequent migratory and differen-
tiation behavior of fresh neurons leaving these matrix zones (migration areas)—to

13
 1. Vertebrate Central Nervous System Development

determine the final morphology of every brain region (Fig. 3). This grid of ma-
trix zones contained longitudinal as well as transverse zones and, ultimately, re-
sulted in a neuromeric bauplan of the brain (see earlier). Because this work was
comparative, the aspect of a common bauplan shared between all vertebrates was
emphasized.

Fig. 3. Schematic transverse view of the developing vertebrate neural tube wall emphasizing local
differences in neural proliferation and migration dynamics and their phenotypic results as viewed
by H. Bergquist and B. Källén (see text).

As already mentioned in the context of neuromery, C.J. Herrick (and his

followers, Ariëns-Kappers, Huber, and Crosby) vigorously attacked this concept,
which seemed to him only to please detail-loving morphologists, deviating from
the functional longitudinal zones considered truly relevant for understanding
brain structure and comparative issues. With regard to searching for homology
of brain structures in different vertebrates, the American school founded the
long-lasting approach of studying functional adult neuronal connectivity using
an increasing number of neuronal tracing substances. To this day, neurobiologists
indeed successfully apply this strategy to the present day. Although powerful
in revealing neuronal connectivity and, thus, delivering arguments for homol-
ogy of central nervous structures among vertebrates, this approach must fail
in cases of similar circuitry that evolved in parallel (homoplastic evolution) in
different species. Another contemporary, L. Edinger, also placed himself against
the ideas of the Swedish school. He instead proposed the sequential addition of
forebrain parts during vertebrate evolution, which is incompatible with an an-
cestral common bauplan. Much in the vein of the Swedish school again was the
“formanalytic approach” of H. Kuhlenbeck (publications between 1926 and 1973;

14
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5. Evolutionary Processes and Evolutionistic
Fancies
In their more elementary aspects the two strands of the organic
and the social, or the hereditary and environmental, as they are
generally called with reference to individuals, run through all human
life and are distinguishable as mechanisms, as well as in their
results. Thus a comparison of the acquisition of the power of flight
respectively by birds in their organic development out of the
ancestral reptile stem some millions of years ago, and by men as a
result of cultural progress in the field of invention during the past
generation, reveals at once the profound differences of process that
inhere in the ambiguous concept of “evolution.” The bird gave up a
pair of walking limbs to acquire wings. He added a new faculty by
transforming part of an old one. The sum total of his parts or organs
was not greater than before. The change was transmitted only to the
blood descendants of the altered individuals. The reptile line went on
as it had been before, or if it altered, did so for causes unconnected
with the evolution of the birds. The aeroplane, on the contrary, gave
men a new faculty without impairing any of those they had previously
possessed. It led to no visible bodily changes, nor alterations of
mental capacity. The invention has been transmitted to individuals
and groups not derived by descent from the inventors; in fact, has
already influenced their careers. Theoretically, it is transmissible to
ancestors if they happen to be still living. In sum, it represents an
accretion to the stock of existing culture rather than a transformation.
Once the broad implications of the distinction which this example
illustrates have been grasped, many common errors are guarded
against. The program of eugenics, for instance, loses much of its
force. There is certainly much to be said in favor of intelligence and
discrimination in mating, as in everything else. There is need for the
acquisition of exacter knowledge on human heredity. But, in the
main, the claims sometimes made that eugenics is necessary to
preserve civilization from dissolution, or to maintain the flourishing of
this or that nationality, rest on the fallacy of recognizing only organic
causes as operative, when social as well as organic ones are active
—when indeed the social factors may be much the more powerful
ones. So, in what are miscalled race problems, the average thought
of the day still reasons largely from social effects to organic causes
and perhaps vice versa. Anthropology is by no means yet in a
position to state just where the boundary between the contributing
organic and social causes of such phenomena lies. But it does hold
to their fundamental distinctness and to the importance of this
distinctness, if true understanding is the aim. Without sure grasp of
this principle, many of the arguments and conclusions in the present
volume will lose their significance.
Accordingly, the designation of anthropology as “the child of
Darwin” is most misleading. Darwin’s essential achievement was that
he imagined, and substantiated by much indirect evidence, a
mechanism through which organic evolution appeared to be taking
place. The whole history of man however being much more than an
organic matter, a pure Darwinian anthropology would be largely
misapplied biology. One might almost as justly speak of a
Copernican or Newtonian anthropology.
What has greatly influenced anthropology, mainly to its damage,
has been not Darwinism, but the vague idea of evolution, to the
organic aspect of which Darwin gave such substance that the whole
group of evolutionistic ideas has luxuriated rankly ever since. It
became common practice in social anthropology to “explain” any part
of human civilization by arranging its several forms in an evolutionary
sequence from lowest to highest and allowing each successive stage
to flow spontaneously from the preceding—in other words, without
specific cause. At bottom this logical procedure was astonishingly
naïve. We of our land and day stood at the summit of the ascent, in
these schemes. Whatever seemed most different from our customs
was therefore reckoned as earliest, and other phenomena disposed
wherever they would best contribute to the straight evenness of the
climb upward. The relative occurrence of phenomena in time and
space was disregarded in favor of their logical fitting into a plan. It
was argued that since we hold to definitely monogamous marriage,
the beginnings of human sexual union probably lay in indiscriminate
promiscuity. Since we accord precedence to descent from the father,
and generally know him, early society must have reckoned descent
from the mother and no one knew his father. We abhor incest;
therefore the most primitive men normally married their sisters.
These are fair samples of the conclusions or assumptions of the
classic evolutionistic school of anthropology, whose roster was
graced by some of the most illustrious names in the science.
Needless to say, these men tempered the basic crudity of their
opinions by wide knowledge, acuity or charm of presentation, and
frequent insight and sound sense in concrete particulars. In their day,
a generation or two ago, under the spell of the concept of evolution
in its first flush, such methods of reasoning were almost inevitable.
To-day they are long threadbare, descended to material for
newspaper science or idle speculation, and evidence of a tendency
toward the easy smugness of feeling oneself superior to all the past.
These ways of thought are mentioned here only as an example of
the beclouding that results from baldly transferring biologically
legitimate concepts into the realm of history, or viewing this as
unfolding according to a simple plan of progress.

6. Age of Anthropological Science

The foregoing exposition will make clear why anthropology is
generally regarded as one of the newer sciences—why its chairs are
few, its places in curricula of education scattered. As an organized
science, with a program and a method of its own, it is necessarily
recent because it could not arise until the biological and social
sciences had both attained enough organized development to come
into serious contact.
On the other hand, as an unmethodical body of knowledge, as an
interest, anthropology is plainly one of the oldest of the sisterhood of
sciences. How could it well be otherwise than that men were at least
as much interested in each other as in the stars and mountains and
plants and animals? Every savage is a bit of an ethnologist about
neighboring tribes and knows a legend of the origin of mankind.
Herodotus, the “father of history,” devoted half of his nine books to
pure ethnology, and Lucretius, a few centuries later, tried to solve by
philosophical deduction and poetical imagination many of the same
problems that modern anthropology is more cautiously attacking with
the methods of science. In neither chemistry nor geology nor biology
was so serious an interest developed as in anthropology, until nearly
two thousand years after these ancients.
In the pages that follow, the central anthropological problems that
concern the relations of the organic and cultural factors in man will
be defined and solutions offered to the degree that they seem to
have been validly determined. On each side of this goal, however,
stretches an array of more or less authenticated formulations, of
which some of the more important will be reviewed. On the side of
the organic, consideration will tend largely to matters of fact; in the
sphere of culture, processes can here and there be illustrated; in
accord with the fact that anthropology rests upon biological and
underlies purely historical science.
 CHAPTER II
FOSSIL MAN

7. The “Missing Link.”—8. Family tree of the Primates.—9. Geological and

glacial time.—10. Place of man’s origin and development.—11.
Pithecanthropus.—12. Heidelberg man.—13. The Piltdown form.—14.
Neandertal man.—15. Rhodesian man.—16. The Cro-Magnon race.—
17. The Brünn race.—18. The Grimaldi race: Neolithic races.—19. The
metric expression of human evolution.

7. The “Missing Link”

No modern zoölogist has the least doubt as to the general fact of
organic evolution. Consequently anthropologists take as their starting
point the belief in the derivation of man from some other animal form.
There is also no question as to where in a general way man’s
ancestry is to be sought. He is a mammal closely allied to the other
mammals, and therefore has sprung from some mammalian type. His
origin can be specified even more accurately. The mammals fall into a
number of fairly distinct groups, such as the Carnivores or flesh-eating
animals, the Ungulates or hoofed animals, the Rodents or gnawing
animals, the Cetaceans or whales, and several others. The highest of
these mammalian groups, as usually reckoned, is the Primate or “first”
order of the animal kingdom. This Primate group includes the various
monkeys and apes and man. The ancestors of the human race are
therefore to be sought somewhere in the order of Primates, past or
present.
The popular but inaccurate expression of this scientific conviction is
that “man is descended from the monkeys,” but that a link has been
lost in the chain of descent: the famous “missing link.” In a loose way
this statement reflects modern scientific opinion; but it certainly is
partly erroneous. Probably not a single authority maintains to-day that
man is descended from any species of monkey now living. What
students during the past sixty years have more and more come to be
convinced of, was already foreshadowed by Darwin: namely that man
and the apes are both descended from a common ancestor. This
common ancestor may be described as a primitive Primate, who
differed in a good many details both from the monkeys and from man,
and who has probably long since become extinct.

Fig. 1. Erroneous (left) and more valid (right) representation of the descent of man.

The situation may be clarified by two diagrams (Fig. 1). The first
diagram represents the inaccurate view which puts the monkey at the
bottom of the line of descent, man at the top, and the missing link in
the middle of the straight line. The illogicality of believing that our
origin occurred in this manner is apparent as soon as one reflects that
according to this scheme the monkey at the beginning and man at the
end of the line still survive, whereas the “missing link,” which is
supposed to have connected them, has become extinct.
Clearly the relation must be different. Whatever the missing link
may have been, the mere fact that he is not now alive on earth means
that we must construct our diagram so that it will indicate his past
existence as compared with the survival of man and the apes. This
means that the missing link must be put lower in the figure than man
and the apes, and our illustration therefore takes on the form shown in
the right half of figure 1, which may be described as Y-shaped. The
stem of the Y denotes the pre-ancestral forms leading back into other
mammalian groups and through them—if carried far enough down—to
the amphibians and invertebrates. The missing link comes at the fork
of the Y. He represents the last point at which man and the monkeys
were still one, and beyond which they separated and became
different. It is just because the missing link represented the last
common form that he was the link between man and the monkeys.
From him onwards, the monkeys followed their own course, as
indicated by the left-hand branch of the Y, and man went his separate
way along the right-hand branch.

8. Family Tree of the Primates

While this second diagram illustrates the most essential elements in
modern belief as to man’s origin, it does not of course pretend to give
the details. To make the diagram at all precise, the left fork of the Y,
which here stands for the monkeys as a group—in other words,
represents all the living Primates other than man—would have to be
denoted by a number of branching and subdividing lines. Each of the
main branches would represent one of the four or five subdivisions or
“families” of the Primates, such as the Anthropoid or manlike apes,
and the Cebidæ or South American monkeys. The finer branches
would stand for the several genera and species in each of these
families. For instance, the Anthropoid line would split into four,
standing respectively for the Gibbon, Orang-utan, Chimpanzee, and
Gorilla.
The fork of the Y representing man would not branch and rebranch
so intricately as the fork representing the monkeys. Many zoölogists
regard all the living varieties of man as constituting a single species,
while even those who are inclined to recognize several species limit
the number of these species to three or four. Then too the known
extinct varieties of man are comparatively few. There is some doubt
whether these human fossil types are to be reckoned as direct
ancestors of modern man, and therefore as mere points in the main
human line of our diagram; or whether they are to be considered as
having been ancient collateral relatives who split off from the main line
of human development. In the latter event, their designation in the
diagram would have to be by shorter lines branching out of the human
fork of the Y.

Fig. 2. The descent of man, elaborated over Figure 1. For further ramifications, see
Figures 3, 4, 9.

This subject quickly becomes a technical problem requiring rather

refined evidence to answer. In general, prevailing opinion looks upon
the later fossil ancestors of man as probably direct or true ancestors,
but tends to regard the earlier of these extinct forms as more likely to
have been collateral ones. This verdict applies with particular force to
the earliest of all, the very one which comes nearest to fulfilling the
popular idea of the missing link: the so-called Pithecanthropus
erectus. If the Pithecanthropus were truly the missing link, he would
have to be put at the exact crotch of the Y. Since he is recognized,
however, as a form more or less ancestral to man, and somewhat less
ancestral to the apes, he should probably be placed a short distance
up on the human stem of the Y, or close alongside it. On the other
hand, inasmuch as most palæontologists and comparative anatomists
believe that Pithecanthropus was not directly ancestral to us, in the
sense that no living men have Pithecanthropus blood flowing in their
veins, he would therefore be an ancient collateral relative of humanity
—a sort of great-great-granduncle—and would be best represented by
a short stub coming out of the human line a little above its beginning
(Fig. 2).
Even this figure is not complete, since it is possible that some of the
fossil types which succeeded Pithecanthropus in point of time, such
as the Heidelberg and Piltdown men, were also collateral rather than
direct ancestors. Some place even the later Neandertal man in the
collateral class. It is only when the last of the fossil types, the Cro-
Magnon race, is reached, that opinion becomes comparatively
unanimous that this is a form directly ancestral to us. For accuracy,
therefore, figure 2 might be revised by the addition of other short lines
to represent the several earlier fossil types: these would successively
spring from the main human line at higher and higher levels.
In order not to complicate unnecessarily the fundamental facts of
the case—especially since many data are still interpreted somewhat
variously—no attempt will be made here to construct such a complete
diagram as authoritative. Instead, there are added reproductions of
the family tree of man and the apes as the lineages have been worked
out independently by two authorities (Figs. 3, 4). It is clear that these
two family trees are in substantial accord as regards their main
conclusions, but that they show some variability in details. This
condition reflects the present state of knowledge. All experts are in
accord as to certain basic principles; but it is impossible to find two
authors who agree exactly in their understanding of the less important
data.

9. Geological and Glacial Time

 A remark should be made here as to the age of these ancestral
forms. The record of life on earth, as known from the fossils in
stratified rocks, is divided into four great periods. The earliest, the
Primary or Palæozoic, comprises about two-thirds of the total lapse of
geologic time. During the Palæozoic all the principal divisions of
invertebrate animals came into existence, but of the vertebrates only
the fishes. In the Secondary or Mesozoic period, evolution progressed
to the point where reptiles were the highest and dominant type, and
the first feeble bird and mammal forms appeared. The Mesozoic
embraces most of the remaining third or so of the duration of life on
the earth, leaving only something like five million years for the last two
periods combined, as against thirty, fifty, ninety, or four hundred million
years that the Palæozoic and Mesozoic are variously estimated to
have lasted.
Fig. 3. The descent of man in detail, according to Gregory (somewhat
simplified). Extinct forms: 1, Parapithecus; 2, Propliopithecus; 3,
Palæosimia; 4, Sivapithecus; 5, Dryopithecus; 6, Palæopithecus; 7,
Pliopithecus; P, Pithecanthropus erectus; H, Homo
Heidelbergensis; N, Homo Neandertalensis.
 Fig. 4. The descent of man in detail, according to Keith (somewhat
simplified). Extinct forms: 2, 5, 6, 7 as in Figure 3; Pith(ecanthropus),
Pilt(down), Neand(ertal). Living forms: Gb, Or, Ch, Go, the anthropoid
apes as in Figure 3.

These last five million years or so of the earth’s history are divided
unequally between the Tertiary or Age of Mammals, and the
Quaternary or Age of Man. About four million years are usually
assigned to the Tertiary with its subdivisions, the Eocene, Oligocene,
Miocene, and Pliocene. The Quaternary was formerly reckoned by
geologists to have lasted only about a hundred thousand years. Later
this estimate was raised to four or five hundred thousand, and at
present the prevailing opinion tends to put it at about a million years.
There are to be recognized, then, a four million year Age of Mammals
before man, or even any definitely pre-human form, had appeared;
and a final period of about a million years during which man gradually
assumed his present bodily and mental type. In this Quaternary period
fall all the forms which are treated in the following pages.
The Quaternary is usually subdivided into two periods, the
Pleistocene and the Recent. The Recent is very short, perhaps not
more than ten thousand years. It represents, geologically speaking,
the mere instant which has elapsed since the final disappearance of
the great glaciers. It is but little longer than historic time; and
throughout the Recent there are encountered only modern forms of
man. Back of it, the much longer Pleistocene is often described as the
Ice Age or Glacial Epoch; and both in Europe and North America
careful research has succeeded in demonstrating four successive
periods of increase of the ice. In Europe these are generally known as
the Günz, Mindel, Riss, and Würm glaciations. The probable
American equivalents are the Nebraskan, Kansan, Illinoian, and
Wisconsin periods of ice spread. Between each of these four came a
warmer period when the ice melted and its sheets receded. These are
the “interglacial periods” and are designated as the first, second, and
third. These glacial and interglacial periods are of importance because
they offer a natural chronology or time scale for the Pleistocene, and
usually provide the best means of dating the fossil human types that
have been or may hereafter be discovered (Fig. 5).

10. Place of Man’s Origin and Development

Before we proceed to the fossil finds themselves, we must note that
the greater part of the surface of the earth has been very imperfectly
explored. Africa, Asia, and Australia may quite conceivably contain
untold scientific treasures which have not yet been excavated. One
cannot assert that they are lying in the soil or rocks of these
continents; but one also cannot affirm that they are not there. North
and South America have been somewhat more carefully examined, at
least in certain of their areas, but with such regularly negative results
that the prevailing opinion now is that these two continents—possibly
through being shut off by oceans or ice masses from the eastern
hemisphere—were not inhabited by man during the Pleistocene. The
origin of the human species cannot then be sought in the western
hemisphere. This substantially leaves Europe as the one continent in
which excavations have been carried on with prospects of success;
and it is in the more thoroughly explored western half of Europe that
all but two of the unquestioned discoveries of ancient man have been
made. One of these exceptional finds is from Africa. The other
happens to be the one that dates earliest of all—the same
Pithecanthropus already mentioned as being the closest known
approach to the “missing link.” Pithecanthropus was found in Java.
Now it might conceivably prove true that man originated in Europe
and that this is the reason that the discoveries of his most ancient
remains have to date been so largely confined to that continent. On
the other hand, it does seem much more reasonable to believe that
this smallest of the continents, with its temperate or cold climate, and
its poverty of ancient and modern species of monkeys, is likely not to
have been the true home, or at any rate not the only home, of the
human family. The safest statement of the case would be that it is not
known in what part of the earth man originated; that next to nothing is
known of the history of his development on most of the continents;
and that that portion of his history which chiefly is known is the
fragment which happened to take place in Europe.
Fig. 5. Antiquity of man. This diagram is drawn to scale, proportionate to the
number of years estimated to have elapsed, as far down as 100,000.
Beyond, the scale is one-half, to bring the diagram within the limits of the
page.

11. Pithecanthropus
 Pithecanthropus erectus, the “erect ape-man,” was determined from
the top part of a skull, a thigh bone, and two molar teeth found in 1891
under fifty feet of strata by Dubois, a Dutch surgeon, near Trinil, in the
East Indian island of Java. The skull and the thigh lay some distance
apart but at the same level and probably are from the same individual.
The period of the stratum is generally considered early Pleistocene,
possibly approximately contemporary with the first or Günz glaciation
of Europe—nearly a million years ago, by the time scale here
followed. Java was then a part of the mainland of Asia.
The skull is low, with narrow receding forehead and heavy ridges of
bone above the eye sockets—“supraorbital ridges.” The capacity is
estimated at 850 or 900 cubic centimeters—half as much again as
that of a large gorilla, but nearly one-half less than the average for
modern man. The skull is dolichocephalic—long for its breadth—like
the skulls of all early fossil men; whereas the anthropoid apes are
more broad-headed. The jaws are believed to have projected almost
like a snout; but as they remain undiscovered, this part of the
reconstruction is conjectural. The thigh bone is remarkably straight,
indicating habitual upright posture; its length suggests that the total
body stature was about 5 feet 7 inches, or as much as the height of
most Europeans.
Pithecanthropus was a terrestrial and not an arboreal form. He
seems to have been slightly more similar to modern man than to any
ape, and is the most primitive manlike type yet discovered. But he is
very different from both man and the apes, as his name indicates:
Pithecanthropus is a distinct genus, not included in Homo, or man.

12. Heidelberg Man

Knowledge of Heidelberg man rests on a single piece of bone—a
lower jaw found in 1907 by Schoetensack at a depth of nearly eighty
feet in the Mauer sands not far from Heidelberg, Germany. Like the
Pithecanthropus remains, the Heidelberg specimen lay in association
with fossils of extinct mammals, a fact which makes possible its
dating. It probably belongs to the second interglacial period, so that its
antiquity is only about half as great as that of Pithecanthropus (Fig. 5).
 The jaw is larger and heavier than any modern human jaw. The
ramus, or upright part toward the socket, is enormously broad, as in
the anthropoid apes. The chin is completely lacking; but this area
does not recede so much as in the apes. Heidelberg man’s mouth
region must have projected considerably more than that of modern
man, but much less than that of a gorilla or a chimpanzee. The
contour of the jaw as seen from above is human (oval), not simian
(narrow and oblong).
The teeth, although large, are essentially human. They are set close
together, with their tops flush, as in man; the canines lack the tusk-like
character which they retain in the apes.
Since the skull and the limb bones of this form are wholly unknown,
it is somewhat difficult to picture the type as it appeared in life. But the
jaw being as manlike as it is apelike, and the teeth distinctly human,
the Heidelberg type is to be regarded as very much nearer to modern
man than to the ape, or as farther along the line of evolutionary
development than Pithecanthropus; as might be expected from its
greater recency. This relationship is expressed by the name, Homo
Heidelbergensis, which recognizes the type as belonging to the genus
man.

13. The Piltdown Form

This form is reconstructed from several fragments of a female brain
case, some small portions of the face, nearly half the lower jaw, and a
number of teeth, found in 1911-13 by Dawson and Woodward in a
gravel layer at Piltdown in Sussex, England. Great importance has
been ascribed to this skull, but too many of its features remain
uncertain to render it safe to build large conclusions upon the
discovery. The age cannot be fixed with positiveness; the deposit is
only a few feet below the surface, and in the open; the associated
fossils have been washed or rolled into the layer; some of them are
certainly much older than the skull, belonging to animals characteristic
of the Pliocene, that is, the Tertiary. If the age of the skull was the third
interglacial period, as on the whole seems most likely, its antiquity
might be less than a fourth that of Pithecanthropus and half that of
Heidelberg man.
The skull capacity has been variously estimated at 1,170, nearly
1,300, and nearly 1,500 c.c.; the pieces do not join, so that no certain
proof can be given for any figure. Except for unusual thickness of the
bone, the skull is not particularly primitive. The jaw and the teeth, on
the other hand, are scarcely distinguishable from those of a
chimpanzee. They are certainly far less human than the Heidelberg
jaw and teeth, which are presumably earlier. This human skull and
simian jaw are an almost incompatible combination. More than one
expert has got over the difficulty by assuming that the skull of a
contemporary human being and the jaw of a chimpanzee happened to
be deposited in the same gravel.
In view of these doubts and discrepancies, the claim that the
Piltdown form belongs to a genus Eoanthropus distinct from that of
man is to be viewed with reserve. This interpretation would make the
Piltdown type more primitive than the probably antecedent Heidelberg
man. Some authorities do regard it as both more primitive and earlier.

14. Neandertal Man

The preceding forms are each known only from partial fragments of
the bones of a single individual. The Neandertal race is substantiated
by some dozens of different finds, including half a dozen nearly
complete skulls, and several skeletons of which the greater portions
have been preserved. These fossils come from Spain, France,
Belgium, Germany, and what was Austro-Hungary, or, roughly, from
the whole western half of Europe. They are all of similar type and from
the Mousterian period of the Palæolithic or Old Stone Age (§ 70-72,
Fig. 17); whereas Pithecanthropus, Heidelberg, and perhaps Piltdown
are earlier than the Stone Age. The Mousterian period may be dated
as coincident with the peak of the last or Würm glaciation, that is,
about 50,000 to 25,000 years ago. Its race—the Neandertal type—
was clearly though primitively human; which fact is reflected in the
various systematic names that have been given it: Homo
Neandertalensis, Homo Mousteriensis, or Homo primigenius.
 The Most Important Neandertal Discoveries

1856 Neandertal Near Skull cap and

Düsseldorf, parts of
Germany skeleton
1848 Gibraltar Spain Greater part of
skull
1887 Spy I Belgium Skull and parts
of skeleton
1887 Spy II Belgium Skull and parts
of skeleton
1889- Krapina Moravia Parts of ten or
1905 more
skulls and
skeletons
1908 La-Chapelle-aux-Saints Corrèze, Skeleton
France including
skull
1908 Le Moustier Dordogne, Skeleton,
France including
skull, of
youth
1909 La Ferrassie I Dordogne, Partial skeleton
France
1910 La Ferrassie II Dordogne, Skeleton
France
1911 La Quina Charente, Skull and parts
France of skeleton
1911 Jersey Island in Teeth
English
Channel

Neandertal man was short: around 5 feet 3 inches for men, 4 feet
10 inches for women, or about the same as the modern Japanese. A
definite curvature of his thigh bone indicates a knee habitually
somewhat bent, and probably a slightly stooping or slouching attitude.
All his bones are thickset: his musculature must have been powerful.
The chest was large, the neck bull-like, the head hung forward upon it.
This head was massive: its capacity averaged around 1,550 c.c., or
equal to that of European whites and greater than the mean of all
living races of mankind (Fig. 6). The head was rather low and the
forehead sloped back. The supraorbital ridges were heavy: the eyes
peered out from under beetling brows. The jaws were prognathous,
though not more than in many Australians and Negroes; the chin
receded but existed.
Some Neandertal Measurements

Skull
Fossil Stature
Capacity
Neandertal 1400 c.c. 5 ft. 4 (or 1)
in.
Spy I 1550 c.c. 5 ft. 4 in.
Spy II 1700 c.c.
La Chapelle-aux-Saints 1600 c.c. 5 ft. 3 (or 2)
in.
La Ferrassie I 5 ft. 5 in.
Average of male Neandertals 1550 c.c. 5 ft. 4 (or 3)
in.
Average of modern European males 1550 c.c. 5 ft. 5 to 8 in.
Average—modern mankind 1450 c.c. 5 ft. 5 in.
Gibraltar 1300 c.c.
La Quina 1350 c.c.
La Ferrassie II 4 ft. 10 in.
Average of modern European 1400 c.c. 5 ft. 1 to 3 in.
females

The artifacts found in Mousterian deposits show that Neandertal

man chipped flint tools in several ways, knew fire, and buried his
dead. It may be assumed as almost certain that he spoke some sort of
language.