Development of the Nervous

System

OTD 341
Dr. Lou Jensen
Fall 2023
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 OTD 341: Neuroanatomy

Unit 1 Unit 2 Unit 3 Unit 4

Session 1: Session 9: Session 14: Session 21:

Organization of Assessments: Electrical Assessments: Thalamus and Hearing &
Nervous System Signaling Internal Capsule Assessments: Balance
Assessments: Exam 2 Neuro Book
Neuroscience
Practice Exam Session 2: Session 10: Club
Session 15: Reflection Session 22:
Exam 1 Development of Sensory Exam 3
Nervous System System
Cranial Nerves Exam 4 Cerebral Cortex

Session 11: Sessions 16 &

Sessions 3 & 4: Session 23:
Neuroplasticity
Spinal Cord 17: Visual Limbic System
& Brainstem System

Session 5: Session 18: Session

Session 12:
Meninges & Cranial Nerve & 24: Blood
Ventricles Pathways Vision Review Supply
Session 6: Session 25:
Session 13: Sessions 19 & 20:
Gross Course
Anatomy ANS & Spinal Motor Systems
Review
Cord
Sessions 7 & 8: Conditions
Begin Finish
Neurons and
with the with the
Glia
BIG BIG
PICTURE PICTURE
! Micro Level (e.g., cells) Meso Level (e.g., systems) Macro Level (e.g., humans in environments !
 Session Objectives
1. Describe the timing and process of neurulation
2. Explain the origin and significance of neural crest cells
3. Describe the sulcus limitans and its significance
4. Name the 3 primary vesicles & 5 secondary vesicles
5. List the adult derivatives of the vesicles & their associated spaces
6. Explain the significance of the pontine and cephalic flexures
7. Describe how spina bifida comes about & the consequences of the
different types of this congenital condition
8. Define anencephaly, craniorachischisis, & holoprosencephaly

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 Introduction to Neurodevelopment
• Why learn about the development of the nervous
system?
1. Understanding development helps us understand the adult
nervous system organization
2. Understanding development helps us understand some
common congenital malformations and diversity in
development
• Neurodevelopment is an amazing phenomenon- billions
of neurons are formed (neurogenesis), migrate to final
destinations, and then begin making connections with
other neurons
• Development of the nervous system is not complete at
birth; myelin, especially, is being created postnatally
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 Neural tube formation (primary neurulation)

1. Chemical signals in 3rd week of embryonic development

lead to formation of neural plate, a thickened portion of
ectoderm
2. Neural plate folds inward to form the neural groove in
the midline with neural folds on each side
3. At the beginning of the 4th week, neural folds fuse in
midline to form the neural tube
4. Entire neural tube is closed by end of 4th week in typical
development

What is the significance of this timeframe?

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Neural tube formation (primary neurulation)
cont.
5. Neural tube gives rise to nearly entire CNS;
cavity inside tube gives rise to ventricular
system (brain) and central canal (spinal cord)
6. As neural tube closes, it separates from
ectoderm (skin) and leaves groups of cells from
crest of neural folds called neural crest cells
– Neural crest cells give rise to a variety of cell types
including much of the PNS: dorsal root ganglia
(sensory neurons), autonomic ganglia, adrenal
medulla, some cranial nerves, etc.

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Neural plate and groove at 18-20 days

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Neural tube closure during 4th week

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Neural crest cells

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 Secondary neurulation
• Once neural tube closes, a secondary
cavity forms into cells caudally during 5th
and 6th weeks
• This forms the sacral spinal cord region

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 Sulcus limitans

Longitudinal groove in wall of neural tube in 4 th

week
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 Sulcus limitans (cont.)
• This separates neural tube, and eventually
brain and spinal cord, into a dorsal half
and a ventral half
– Dorsal to sulcus limitans is the alar plate and
this has sensory functions
– Ventral to sulcus limitans is the basal plate
and this has motor functions

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 Embryonic vesicles & flexures
• Bulges and
bends appear in
the neural tube
near the rostral
end
• During 4th week,
3 bulges, or
primary
vesicles, are
present in
neural tube

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During 5th week, 5 secondary vesicles
are apparent

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 *Adult derivatives of vesicles (Table 2-1)
Primary Vesicle Secondary Vesicle Neural Derivatives Cavity

Prosencephalon Telencephalon Cerebral hemispheres Lateral ventricles

(forebrain)

Diencephalon Thalamus, 3rd ventricle

hypothalamus, retina,
etc.

Mesencephalon Mesencephalon Midbrain Cerebral aqueduct

(midbrain)

Rhombencephalon Metencephalon Pons, cerebellum Part of 4th ventricle

(hindbrain)

Myelencephalon Medulla Parts of 4th ventricle

and central canal

https://youtu.be/Tp25wrm-AoA
Flexures in the neural tube
– Cervical flexure:
between future
brainstem and spinal
cord; straightens later
in development
– Cephalic flexure:
between future
midbrain and
diencephalon; persists
in adulthood and is the - Pontine flexure: between
reason for “the bend” future pons and medulla;
in the neural axis does not persist but affects
caudal brainstem 17
Pontine flexure: does not persist but affects
caudal brainstem

Sulcus limitans separates alar and basal plates as pontine

flexure flattens neural tube
Thus, in this part of the future brainstem (pons and medulla),
the sensory neurons are lateral to the medial motor neurons

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 Growth of the telencephalon
• Two swellings arise and
fold over so that the
telencephalon and
diencephalon fuse
• These swellings are the
future cerebral
hemispheres

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 Growth of the telencephalon (cont.)
• Viewed laterally
• Diencephalon
now deep to
telencephalon
• Telencephalon
curves into a
C-shape
• Significance?

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Folding over of hemispheres is what makes
the insula hidden in the adult brain

Brain of infant born at

26 weeks’ gestation

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 Other CNS developmental events

1. 3rd-5th months: neurons and glial cells

continue to form and migrate
2. Synaptogenesis begins shortly beyond
this and continues postnatally
3. Myelination occurs mostly postnatally
4. Cerebral cortex initially smooth, but
beginning at 24 weeks convolutions begin
to appear and increase in number
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 Progressive development of cortical
convolutions and increased brain volume

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 Human Neurodiversity Should
Be Celebrated!
• https://youtu.be/aWxmEv7fOFY

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Big idea!
Atypical events during development
• Atypical prenatal development can occur due to genetics,
chromosomal issues, infections, exposure to medications,
chemicals, or other agents, environment, etc.
– Teratogens: drugs or other agents that cause atypical development
• Environment (e.g., pollution), drugs, alcohol
• Timing
• Genetics of fetus or mother
– Nutrition
– Stress
– Maternal age
– Paternal factors affecting sperm
• About 15% of all known pregnancies end in miscarriage, usually
during first 12 weeks due to a major anomaly in the formation of the
structures of the embryo

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 Atypical development of the neural tube

• Craniorachischisis: complete failure of neural tube to

close; incompatible with life
• Spina bifida: partial failure of neural tube to close
(different types range from mild to severe); some examples:
– Spina bifida occulta: atypical formation of vertebral column only
– Meningocele: herniation of meninges only
– Myelomeningocele: herniation of spinal cord and meninges
• Anencephaly: failure of rostral end of tube to close
resulting in absent cerebral hemispheres; incompatible
with life
– http://www.cbsnews.com/news/baby-born-missing-most-of-brain-celebrates-first-
birthday

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 Atypical development of the neural tube
(continued)
• Neural tube atypicalities can be detected by ultrasound
or elevated levels of alpha-fetoprotein in blood
• Neural tube closure dependent on adequate folic acid in
mother’s diet

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 Spina bifida
(1 in 1000 live births)

www.nytimes.com/imagepages/2007/08/01/health/adam/19087Spinabifidadegreesofseverity.html
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Holoprosencephaly: partial or complete
failure of prosencephalon to separate into
diencephalon and telencephalon; usually
fatal, but milder forms are compatible with
life

Figure 2-20 A, Anterior view of the brain of a 20-week fetus with a severe form of holoprosencephaly in which the
fissure normally present between the hemispheres is completely missing. B, Newborn with a slightly less severe
form of holoprosencephaly. Part of the longitudinal fissure is present (red arrow), but cortex continues across the
midline (blue arrow), the corpus callosum is missing, a single lateral ventricle spans the midline (green arrow),
and the diencephalon is fused into a single structure. (Courtesy Dr. Jeffrey A. Golden, University of Pennsylvania
School of Medicine.)
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Facial atypicalities are commonly present with
holoprosencephaly (HPE), as this time of
neurodevelopment is also when facial structures
are being formed.

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 Other neurodevelopmental
complications
• Later fetal development can be disrupted
by atypical neuronal proliferation and
migration
• Fetal alcohol spectrum disorder (FASD)
– Most common cause of intellectual disabilities and the
leading preventable cause of congenital
malformations in the United States

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Fetal alcohol syndrome

http://www.judiciaryreport.com/images/fas-brain.jpg 33
• http://www.nytimes.com/2016/08/24/health/zika-a-formidable-enemy-attacks
-and-destroys-parts-of-babies-brains.html?_r=0

• https://www.cdc.gov/zika/healtheffects/birth_defects.html

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 Congenital Zika Syndrome
• Severe microcephaly and skull partially collapsed
• Damage to eyes and brain areas for vision
• Hydrocephaly
• Damage may continue after birth
• Brain areas targeted: corpus callosum, cerebellum, basal
ganglia
• Many infections cause calcification in the brain; Zika
calcification occurs at gray matter – white matter junction
• This junction is critical for brain formation as healthy cells
here release chemicals that allow neurons to migrate to
their intended destination
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Major congenital Functional defects & minor 36
abnormalities in red abnormalities in gold
About 5 – 6 weeks

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7 to 8 weeks

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56 days or 8 weeks embryo becomes a
fetus

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40 weeks: The newborn

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 Resources
• The Neurodevelopment Timeline activity posted on the course
website is a great way to learn neurodevelopment!
• Check out Baby’s Brain: Wider than the Sky from the PBS series
The Secret Life of the Brain. This is available to you (optional) on
the course website. If you like documentaries, learning about
preemies, or are just fascinated by the brain, be sure to watch this!
Here are some short video clips to serve as teasers:
http://www.pbs.org/wnet/brain/episode1/index.html
• The National Institute for Neurological Disorder and Stroke is a
wonderful resource and has useful information about
holoprosencephaly (HPE):
https://www.ninds.nih.gov/Disorders/All-Disorders/Holoprosencephal
y-Information-Page
• Another website for more in depth HPE information and images is:
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hpe-
overview
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 References
• Blumenfeld, H. (2002). Neuroanatomy through clinical cases.
Sinauer Associates.
• McNeill, M. E. (1997). Neuroanatomy primer. Lippincott Williams &
Wilkins.
• Vanderah, T. W., & Gould, D.J. (2021). Nolte‘s the human brain: An
introduction to its functional anatomy (8th ed.) Elsevier.

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