Morphogenesis
Competencies:
- Identify the three primary vesicles and their five derivatives during development.
- Relate the molecules emphasized in class with the development they regulate.
- Describe the result of developmental defects, such as failure to close the caudal or rostral neuropores.
To master
the material presented in this lecture:
Read ...
Purves text, Chapter 22 and pp 744
Haines pp 184.
Check
out ... This cool
website:
Look at the Review Questions below ...
Listen
to the lecture and focus on the following points ...
Review Embryology lecture on "The bilaminar and trilaminar
embryo" - Dr. Pescatelli
Ectoderm
is one of the 3 primary germinal cell layers in the 2 week old embryo; Induction,
Proliferation and Differentiation of Ectoderm into:
- Cutaneous
Ectoderm, Neuroectoderm
- formed by induction of the epithelium in the neural plate)
- Neural
tube and cerebral vesicles - Central Nervous System (CNS)
- Neural
crest and cellular derivatives - Peripheral Nervous System (PNS)
Development
of the neural plate
- Primitive
(Hensen’s) node
- Primitive
streak
- Notochord
- Three Primary
germ layers
- Ectoderm
- Mesoderm
- Endoderm
- Three Brain
regions
- Forebrain
- Midbrain
- Hindbrain
Neural
plate and encephalization
- The
search for "the neural inducer" yields several Nobel
prizes.
Molecules
Important in Development
- Regulatory
Genes (DNA)
- Expressed
in cascades throughout development
e.g., Induction ~ Neural plate; Neurulation ~ Neural tube
- Dors-vent
axis defined by Sonic hedgehog (Shh) gene
- Segmentation
defined by Homeobox (Hox) genes
- Proneural
genes (e.g. atonal) involved in differentiation
- Transcription
factors (Proteins and polypeptides)
- Transcription
factors also expressed in cascades
e.g., Bone morphogenetic proteins (BMPs) produce epidermal
tissue unless blocked by 3 other genes, follistatin, chordin
and noggin
- Neurotrophins
(Growth factor family)
- Nerve
growth factor (NGF) - 1st growth factor discovered
Subsequently found to be specific for only certain classes
of neurons (e.g. sympathetic ganglion cells and cholinergic
CNS neurons) - receptor is TrkA
- Brain-derived
neurotrophic factor (BDNF) and NT4/5
Specific for sensory ganglion neurons - receptor is TrkB
- Neurotrophin
3 (NT-3)
Specific for all ganglion cells - receptor is TrkC
- Vitamins
(Retinoic acid (RA - high concentration in Hensen’s node)
- Neural
patterning (Differentiation) ~ different parts of nervous
system
- Gradients
of RA important in expression of developmental genes (Hox
genes)
- Cell
adhesion molecules (e.g., E- and N-cadherins)
- Important
in cell migration and axonal outgrowth
Expression
domains of genes responsible for Neurulation
- Sonic
hedgehog (Shh) - important for establishing dorsal-ventral axis
- Engrailed
(En) and Paired (Pax) - important for proper cerebellum development
- Wnt-1
and Fgf 8 - important for normal midbrain development
Neurulation
- Neural
groove, folds, tube
- Notochord
Neural
tube closure (E18-E23)
- Anterior
and posterior neuropores
- Somites
Cranial
and caudal neuropores
- Amniotic
cavity
- Neural
canal
Derivatives
of cephalad neural plate
- The
cerebral vesicles of the CNS:
- Prosencephalon
- Telencephalon (lateral ventricles)
- Diencephalon (third ventricle)
- Mesencephalon
(cerebral aqueduct of Sylvius; iter)
- Rhombencephalon
(fourth ventricle)
- Metencephalon
- Myelencephalon
Flexures
and cerebral vesicles E28
- Cervical
flexure
- Mesencephalic
flexure
- Pontine
flexure and vesicles E3
Rhombomeres
and Cranial Nerve Placodes
- Rhombomeres
1-8
- Branchial
arches
- Cranial
nerve roots derived from placodes
- Homeobox
genes
- Homeotic
mutants
Cerebral
hemisphere development at E50
- Cerebellum
derived from rhombic lip
Summary
of cerebral vesicle and ventricular development
| Vesicle |
Ventricular
component |
| Telencephalon |
Lateral
ventricles |
| Diencephalon |
Third
ventricle |
| Mesencephalon |
Cerebral
aqueduct (of Sylvius) or iter |
| Metencephalon |
Fourth
ventricle |
| Myelencephalon |
Central
canal |
Cytogenesis
in Neural Epithelium
- External
and internal limiting membranes
- Neuroepithelial
precursor cell
Neurogenesis/Cytogenesis
- Neuroepithelial
precursor cells in marginal layer
- Neuroblasts
and glioblasts in mantle layer
- Mitotic
cells and ependymal cells in ventricular layer
Spinal
cord neurogenesis
- Neurons
derived from neuroblasts
- Glia
derived from glioblasts
- Microglia
derived from mesenchymal cells
- Ependymal
cells - some remain pluripotential throughout life
Functional
morphology and organization of spinal cord neurons
- Alar
and basal plates
- Sulcus
limitans
- Roof
and floor plates
Derivatives
of the neural crest
- Dorsal
root ganglion
- Pseudounipolar
ganglion cells
- Satellite
cells
- Schwann
cells (for peripheral myelin)
- Postganglionic
sympathetic visceral efferents
- Adrenal
medulla (chromafin cells)
- Postganglionic
parasympathetic visceral efferents
Spina
bifida: a defect in development
- Spina
bifida occulta
- Meningocoele
- Meningomyelocoele
- Myeloschisis
/ rachischisis
- Pax-3
null mutants exhibit spina bifida, lack of dorsal root ganglia
and neural crest derivatives
Consider the Following Questions ...
- Neural crest arises from what layer of the embryo, and gives rise to what cells in the PNS, in the gut and in the skin?
- During development of the CNS we speak of "encephalization", what does this mean?
- Describe the derivatives of the prosencephalon and rhombencephalon.
- Failure to close the anterior neuropore would take place at what embryonic age, and result in what clinical syndrome?
- Why is Vitamin A important for normal development?
- Describe three gene products important for normal morphogenesis?
