Neurodevelopment Notes
Week 1&2: Development of the Nervous System
Neural Induction
1. Evolutionary perspectives:
Neurons throughout the evolution of multicellular organisms have had many features
in common.
The first basic (early) body plan is similar among species.
Animal models: C. elegans, Drosophila, Zebrafish, Hydra
Differences in behavior steered by the nervous system based on needs & environment.
*All nervous tissue is derived from the ectoderm. (Mainly the skin)
2. Derivation of neural tissue
The nervous system shares a common cellular lineage with the ectoderm
C. elegans:
~1000 cells in total, 302 neurons exactly.
The AB blastomere gen both skin (=hypodermis) and the nervous system.
During gastrulation (Formation of 3 germ layers):
The next phase (=proliferation phase) in the dev of C.elegans also highlights the shared
lineages of hypodermis and neurons.
The neurons are primarily derived from the ventrolateral surface, through the divisions of
the AB progeny cells and migrate into the interior to form rings. (Complete in 2 days)
,Drosophila
The nervous system of Drosophila is derived from the ventrolateral region of the ectoderm.
1. Invagination of the ventral furrow (mesoderm moves to the inside)
2. Involution of the mesoderm at the ventral surface brings the neurogenic region
closer to the midline -> neuroblasts enlarge -> migrate to interior -> neurons and
glia will form nerve cords.
*The neuroblasts separate from the ectoderm by delamination. The delaminated
neuroblasts then gen several neurons (incl Ganglion Mother Cell) thru a stereotypic
pattern of asymmetric cell divisions.
Xenopus:
1. The involuting cells form mesodermal tissue and induce the cells of
the overlying ectoderm to dev into neural tissue (labeled as
neurogenic region)
2. The neurogenic region forms the neural plate and is now restricted
to give rise to neural tissue.
*Neuroectoderm gives rise to brain and spinal cord.
3. Induction of the neural tissue
Neurulation:
1. Neural plate begins to roll up, forms the neural walls which fuse at the
dorsal margins to form the neural tube.
2. A group of cells known as neural crest cells arises at the point of
fusion of the neural tube
Experimental studies reveal the interactions with neighboring tissues in making neural
tissue:
Isolation of fragments of embryos at diff dev stages show when tissue bec committed
to the neural lineage (= lineage arises during gastrulation)
The molecular nature of the neural
inducer:
Interactions b/w the animal and
vegetal cells of the amphibian
embryo are necessary for
induction of the mesoderm
Indirect & Direct neural induction:
*The involuting mesoderm has
the capacity to induce neural
tissue formation
, 1. Identification of noggin as a neural inducer:
- Noggin gene induces neural tissue from isolated animal caps, without any induction of
mesodermal genes
2. Chordin gene is another organizer molecule that induces neural tissue
3. Activin (can bind follistatin):
- Expression of a truncated (shortened at end) activin receptor blocks normal signaling
thru the receptor and induces neural tissue
Dissociation of animal cap cells prior to gastrulation causes most of cells to differentiate
into neurons in culture (Neural fate is actively suppressed by cellular assoc in
ectoderm)
Vertebrates and Invertebrates show similar mol to pattern the dorsal-ventral axis
e.g Drosophila embryo cross section resembles an inverted Xenopus embryo.
*Loss of noggin and chording in dev mice causes severe defects in head development.
Chordin, noggin and follistatin (released by mesodermal cells) all interfere
with the activation of BMP receptors by the BMPs in the ectoderm and block
the anti-neutralizing effects of BMP4.
Therefore, they induce this region to develop as neural tissue -> gen brain, spinal
cord and most of PNS.
Noggin binds several BMPs with higher affinity => blocks BMP signaling
Polarity & Segmentation:
1. Regional identity of the nervous system:
2. The anterior-posterior axis and Hox genes (Example: Drosophila)
Mechanisms that control the regional dev of the CNS dep on the mechanism that initially
set up the A-P axis of the embryo.
- Cytoplasmic polarity (Gradient) -> Reg the expression of Gap genes-> reg the expression
of pair-rule genes
- Then the pair rule genes reg the expression of segment polarity genes and homeotic
genes that lead to the unique dev of each segment!
Elimination of the Hox gene cluster results in all segments dev an identical morphology
=> Hox genes are imp in the development of positional identity in animals
+ Hox gene clusters in arthropods and vertebr have a similar spatial organiz and order
along chromosomes!
3. Hox gene function in the nervous system
Week 1&2: Development of the Nervous System
Neural Induction
1. Evolutionary perspectives:
Neurons throughout the evolution of multicellular organisms have had many features
in common.
The first basic (early) body plan is similar among species.
Animal models: C. elegans, Drosophila, Zebrafish, Hydra
Differences in behavior steered by the nervous system based on needs & environment.
*All nervous tissue is derived from the ectoderm. (Mainly the skin)
2. Derivation of neural tissue
The nervous system shares a common cellular lineage with the ectoderm
C. elegans:
~1000 cells in total, 302 neurons exactly.
The AB blastomere gen both skin (=hypodermis) and the nervous system.
During gastrulation (Formation of 3 germ layers):
The next phase (=proliferation phase) in the dev of C.elegans also highlights the shared
lineages of hypodermis and neurons.
The neurons are primarily derived from the ventrolateral surface, through the divisions of
the AB progeny cells and migrate into the interior to form rings. (Complete in 2 days)
,Drosophila
The nervous system of Drosophila is derived from the ventrolateral region of the ectoderm.
1. Invagination of the ventral furrow (mesoderm moves to the inside)
2. Involution of the mesoderm at the ventral surface brings the neurogenic region
closer to the midline -> neuroblasts enlarge -> migrate to interior -> neurons and
glia will form nerve cords.
*The neuroblasts separate from the ectoderm by delamination. The delaminated
neuroblasts then gen several neurons (incl Ganglion Mother Cell) thru a stereotypic
pattern of asymmetric cell divisions.
Xenopus:
1. The involuting cells form mesodermal tissue and induce the cells of
the overlying ectoderm to dev into neural tissue (labeled as
neurogenic region)
2. The neurogenic region forms the neural plate and is now restricted
to give rise to neural tissue.
*Neuroectoderm gives rise to brain and spinal cord.
3. Induction of the neural tissue
Neurulation:
1. Neural plate begins to roll up, forms the neural walls which fuse at the
dorsal margins to form the neural tube.
2. A group of cells known as neural crest cells arises at the point of
fusion of the neural tube
Experimental studies reveal the interactions with neighboring tissues in making neural
tissue:
Isolation of fragments of embryos at diff dev stages show when tissue bec committed
to the neural lineage (= lineage arises during gastrulation)
The molecular nature of the neural
inducer:
Interactions b/w the animal and
vegetal cells of the amphibian
embryo are necessary for
induction of the mesoderm
Indirect & Direct neural induction:
*The involuting mesoderm has
the capacity to induce neural
tissue formation
, 1. Identification of noggin as a neural inducer:
- Noggin gene induces neural tissue from isolated animal caps, without any induction of
mesodermal genes
2. Chordin gene is another organizer molecule that induces neural tissue
3. Activin (can bind follistatin):
- Expression of a truncated (shortened at end) activin receptor blocks normal signaling
thru the receptor and induces neural tissue
Dissociation of animal cap cells prior to gastrulation causes most of cells to differentiate
into neurons in culture (Neural fate is actively suppressed by cellular assoc in
ectoderm)
Vertebrates and Invertebrates show similar mol to pattern the dorsal-ventral axis
e.g Drosophila embryo cross section resembles an inverted Xenopus embryo.
*Loss of noggin and chording in dev mice causes severe defects in head development.
Chordin, noggin and follistatin (released by mesodermal cells) all interfere
with the activation of BMP receptors by the BMPs in the ectoderm and block
the anti-neutralizing effects of BMP4.
Therefore, they induce this region to develop as neural tissue -> gen brain, spinal
cord and most of PNS.
Noggin binds several BMPs with higher affinity => blocks BMP signaling
Polarity & Segmentation:
1. Regional identity of the nervous system:
2. The anterior-posterior axis and Hox genes (Example: Drosophila)
Mechanisms that control the regional dev of the CNS dep on the mechanism that initially
set up the A-P axis of the embryo.
- Cytoplasmic polarity (Gradient) -> Reg the expression of Gap genes-> reg the expression
of pair-rule genes
- Then the pair rule genes reg the expression of segment polarity genes and homeotic
genes that lead to the unique dev of each segment!
Elimination of the Hox gene cluster results in all segments dev an identical morphology
=> Hox genes are imp in the development of positional identity in animals
+ Hox gene clusters in arthropods and vertebr have a similar spatial organiz and order
along chromosomes!
3. Hox gene function in the nervous system
