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Lecture 5: Neurulation
Seung K. Kim
Dept. of Developmental Biology
DB201 Development & Disease Mechanisms
.
Summary of cell movements in gastrulation
Mitchell and Sharma, Embryology, An Illustrated Colour Text 2005)
Formation of the primitive streak
Lodish, Molecular
Cell Biology 2006
•
•
•
Establishing bilateral symmetry
Beginning of A-P axis
Initiating formation of endoderm and mesoderm and
ectoderm
The node breaks bilateral symmetry to form the L-R axis
Figure 22-87a Molecular Biology of the Cell (© Garland Science 2008)
Sagittal schematic of human gastrula
Langman’s Medical Embryology 11th Edition
Fates of different mesoderm subdivisions
Dorsal
Ventral
Neurulation
Neurulation
• Neurulation refers to the folding process in vertebrate embryos,
which includes the transformation of the neural plate into the
neural tube. The embryo at this stage is termed the neurula.
• Begin the patterning of neural differentiation along the D-V, A-P
and radial (proximo-distal) axes
• Create and disseminate neural crest cells
• Later, establish the important architectural features of the hindmid- and forebrain, with closure of the neural tube
Stages of spinal cord development in neurulation
From Jessel, Nature Reviews Genetics
Copp et al 2003 Nature Reviews Genetics
Figure 22-79 Molecular Biology of the Cell (© Garland Science 2008)
Overview of neural tube development and closure
Central nervous system function is required
for ingestion of amniotic fluid, a biomarker
Normal amniotic fluid levels
on trans-abdominal ultrasound
Polyhydramnios on
trans-abdominal ultrasound
Neural tube defects
Development of dorsal-ventral
asymmetry in neurogenesis
Primitive streak regression
and notochord growth
Possible modes of inductive signaling
Dorsal ventral polarization
in fetal spinal cord architecture
Dorsal root ganglion [DRG] sensory neurons, commisural [C] and
accessory neurons [A] are dorsal
Motor neurons [M] and ventral interneurons [V] are ventral
From Jessel, Nature Reviews Genetics
Sonic hedgehog (Shh) is a morphogen
produced in the notochord and floor plate
Jessel, Nature Reviews Genetics
Figure 22-80a Molecular Biology of the Cell (© Garland Science 2008)
Figure 22-80 Molecular Biology of the Cell (© Garland Science 2008)
Fates of different mesoderm subdivisions
Dorsal
Ventral
Regulation of somite
differentiation along the dorsal
ventral axis. Arrows show known
signals controlling somite cell
fates, including Sonic hedgehog
(Shh) and neurotrophin 3 (NT-3)
and Wnt from the ‘roof plate’ of
the neural tube. The later fates of
subsets of some somite cells are
also shown.
We will see in the next lecture
how the notochord is an organizer
of neural development.
Development of anterior-posterior
asymmetry in neurogenesis
Note: A-P = rostral-caudal
HOX genes and establishment of anterior-posterior polarity
Figure 22-46 Molecular Biology of the Cell (© Garland Science 2008)
Figure 22-97 Molecular Biology of the Cell (© Garland Science 2008)
Hox genes regulate neural crest cell migration into the arches
We will see
this again
when we cover
head and neck
development in
a later lecture
Neural crest cells and progeny migrate and
populate diverse tissues and organs
Neural crest cell lineage and progeny
Gilbert, Developmental
Biology, 2009
Waardenburg syndrome from mutations in
Pax3, a transcription factor in neural crest cells
1. Skin: Partial albinism
2. Hair: White forelock, white eye lashes, premature graying of hair
(sometimes called ‘Piebaldism’
3. Eyes: Laterally displaced inner canthi
4. Ears: Cochlear deafness
5. Nose: Wide nasal bridge
6. Mouth: Cleft lip/palate, bilateral cleft lip
7. GI: Hirschsprung disease occasionally (loss of ganglia from gut)
8. Neuro: Spina bifida, lumbosacral myelomeningocele
Human brain development
and subdivision by ‘vesicles’
Moore & Persaud 2003
Development along the
radial axis in neurogenesis
Neural stem cells
Meninges
derived from Semaphorins from meninges
mesoderm and
NC cells
Figure 22-98 Molecular Biology of the Cell (© Garland Science 2008)
Layering in the cortex and elsewhere reflects ‘birth’ order
Figure 22-99 Molecular Biology of the Cell (© Garland Science 2008)
Summary
• Neurulation refers to the folding process in vertebrate embryos,
which includes the transformation of the neural plate into the
neural tube. The embryo at this stage is termed the neurula.
• Begin the patterning of neural differentiation along the D-V, A-P
and radial (proximo-distal) axes
• Create and disseminate neural crest cells
• Later, establish the important architectural features of the hindmid- and forebrain, with closure of the neural tube
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