1. Formation and patterning of the nervous system
I. Neural Induction and Neurulation - specification of neural fate and formation of the neural tube. Delamination of neural crest cells.
II. Neural Patterning - patterning of neural progenitors along the dorsoventral and anteroposterior axis
III. Neurogenesis - differentiation of neural progenitors into postmitotic neurons and glia.
IV. Understanding neural patterning in the context of neurogenesis

2. I. Neural Induction and Neurulation - specification of neural fate and formation of the neural tube.
NEURAL INDUCTION : the delineation of ectodermal cells to the neural fate.
NEURULATION: the process in which the ectoderm of the future brain and spinal cord - the neural plate - develops folds (neural folds) and forms the neural tube.

3. that divert them to alternative fates.
The neural plate
Neural induction constitutes the initial step in the generation of the vertebrate
nervous system, whereby embryonic ectodermal cells are exposed to signals that
will instruct the cells to become neural progenitor cells unless exposed to signals
that divert them to alternative fates.

4. Symmetric division and interkinesis of neuroepithelial cells

5. Neurulation - formation of the neural tube.
24 hrs
a-b. neural plate has just formed and undergoing shaping
B-D. bending of the neural plate, formation of neural folds and subsequent elevation and convergence of these folds toward the dorsal midline
D. Bending is initiated at the midbrain junction and progresses both rostrally and caudally. THIS OCCURS VIA A TWO STEP PROCESS REFERRED TO AS BENDING AND FOLDING. -

6. Mechanics of neurulation: bending and folding at distinct locations
Bending occurs at 3 hinge pts:
Median hinge point -over the prechorda
Plate
Paired dorsolateral hinge points
Folding involves the rotation of the
Plate around the hinge points,
Folding around the mhp is called elevation
Folding around the dlhps is called conversion

7. Mechanics of neurulation: bending and folding at distinct locations
Median Hinge point is induced by signals from the notochord, experiments in mouse that Shh
signaling that comes from the notochord inhibits DHP formation, if Shh is over-
expressed (in transgenic mice or Ptc mutants) Dorsal hinge points do not form
resulting in neural tube defects.
The epidermal ectoderm, folding at the DLHP fails to occur if epidermal ectoderm is removed.

8. Four Key events in formation and morphogenesis of neural folds.
The structure of the neural folds, the interface between the neural plate and lateral ectoderm, binds the two layers together, aid in the bending of the neural plate.
IE. If lateral ectoderm is removed the neural plate will not fold properly.

9. Cooperative (hinge point) model.
Neural plate is firmly anchored to adjacent tissues at hinge points (to the notochord for MHP and
Epidermal ectoderm for the DLHP.
2. Neuroepithelial cell wedging within the hinge-points generates furrowing.
3. Forces for folding are generated lateral to the hinge points by the expanding epidermal ectoderm.

10. Fusion of the neural folds
Cellular protrusions extend from apical cells on the neural folds as they approach one another in the dorsal midline and interdigitate as the folds come into contact.

11. Fusion of the neural folds
The fusion and subsequent separation of the neural tube and surface ectoderm results from differential adhesion of the two tissue types. The neural tube expresses N-CAM and
N-cadherin whereas the surface ectoderm expresses E-cadherin.
No separation of the neural tube occurs when one side of the frog embryo is injected with N-cadherin RNA, so that N-Cadherin is expressed in the epidermal cells as well as presumptive neural tube.

12. The rostral-caudal sequence of neurulation in mouse
Begins with neural tube Closure 1:
Initiated at hindbrain/cervical boundary
At 7 somite stage and spreads rostrally
and caudally from this site.
A second de novo closure event
Closure 2 occurs at the forebrain/midbrain
Boundary and closure also initiates at
rostral extreme of the forebrain Closure 3

13. The rostral-caudal sequence of neurulation in mouse
Secondary neurulation : at more caudal level the neural tube is formed in the tail bud, without neural folding. The tail bud is
Comprised of retreating primitive streak.
Mesenchymal cells of the dorsal part of the tail bud undergo condensation and epithlialization to form a secondary neural tube, the lumen of which is continuous with that of the primary neural tube.

14. Secondary Neurulation - vulnerable target for neural tube defects

15. I. Neural Induction and Neurulation - specification of neural fate and formation of the neural tube.
NEURAL INDUCTION : the delineation of ectodermal cells to the neural fate.
NEURULATION: the process in which the ectoderm of the future brain and spinal cord - the neural plate - develops folds (neural folds) and forms the neural tube.