CNS/PNS; neural tube development

Question 1

What happens after gastrulation?

Answer 1

Neurulation!

Question 2

Neurulation

Answer 2

after gastrulation (when germ layers are established) ectoderm forms three basic derivations by subdivision. The embryo is now called a neurula. pattering is dependent upon BMP signaling events

Question 3

neurulation – high levels of BMP

Answer 3

makes epidermis

Question 4

neurulation – low levels of BMP

Answer 4

makes neural plate (neural induction by the organizer works through BMP antagonism)

Question 5

neurulation in frogs

Answer 5

• induction forms neural plate on the ectodermal surface
  -this change in fate is characterized by the expression of Sox transcription factors –> promotes neural gene expression while repressing BMPs
• morphogenetic movements causes the formation and upward movement of neural folds at the plate/epidermis boundary
  -fusion of the neural folds internalizes the neural plate, forming the hollow neural tube
  -this process is referred to as primary neurulation (from ectoderm)

Question 6

Sox transcription factors

Answer 6

promotes neural gene expression while repressing BMPs

Question 7

neurulation in the chick (at 24 hrs)

Answer 7

-similar to gastrulation, neurulation is temporally (related to the passage of time) different along the anterior/posterior axis
-at this point, neurulation is almost complete in the anterior while gastrulation is still underway in the posterior
-although out focus is on neural development, changes are happening to underlying mesoderm and endoderm at the same time

Question 8

primary neurulation

Answer 8

During primary neurulation, the original ectoderm is divided into three sets of cells: (1) the internally positioned neural tube, which will form the brain and spinal cord, (2) the externally positioned epidermis of the skin, and (3) the neural crest cells AND the process by which the neural tube, the precursor of the brain and spinal cord, is shaped from the neural plate

-basal chordates only exhibit this and not secondary neurulation

Question 9

secondary neurulation

Answer 9

in vertebrates, this is when caudal neural tube arises from mesenchyme
- primary and secondary neural tubes fuse at the transition zone
-junctional neurulation occurs in this zone that features partial use of both mechanisms

Question 10

primary neurulation’s 4 steps

Answer 10

1. elongation and folding
2. bending of the neural plate
3. convergence of neural folds
4. closure of the neural tube

Question 11

Step 1. elongation and folding

Answer 11

cells of the neural plate elongate onto columnar cells and fold upward bilaterally around the medial hinge point (MHP); this forms the neural groove

Question 12

Step 2. bending of the neural plate

Answer 12

bending of the neural plate downward at the epidermal junction to form the neural folds

Question 13

Step 3. convergence of the neural folds

Answer 13

convergence of the neural folds occurs when a portion of the neural plate contacts the overlying epidermis; this region is called the dorsolateral hinge point (DLHP). shape changes at the DLHP bend the neural folds toward the midline

Question 14

Step 4. closure of the neural tube

Answer 14

closure of the neural tube occurs when the neural folds make contact at the midline. neural plate cells unite to close the neural tube while epidermal cells unite to form contiguous dorsal epidermis. neural crest cells in-between disperse as mesenchyme

Question 15

Expression of alternative adhesion molecules drives separation of neural tube and epidermis

Answer 15

-ectoderm epithelia express E-cadherin
- ectoderm cells becoming neural plate down regulate E-cadherin and begin expressing N-cadherin instead
-because catherine binding is homotypic, epidermal and neural cells no longer bind each other, so they de-adhere (associations become loose)
-when neural folds make contact, homotypic catherine binding drives reunification of both epithelial types (neural and epidermal) along the midline

Question 16

E-cadherin

Answer 16

epithelial cadherin (transmembrane proteins that mediate cell–cell adhesion in animals)

Question 17

N-cadherin

Answer 17

neural catherine (transmembrane proteins that mediate cell–cell adhesion in animals)

Question 18

grainy head transcription factors

Answer 18

partially control the separation process of neural tube and epidermis; grainy head- like 2 is required to down regulate E-cadherin expression in neural folds, and mutations in mouse Grainyhead-2 and -3 cause many neural tube defects

Question 19

Patterning the neural tube along the A/P axis

Answer 19

• the anterior neural tube begins forming three regions called primary vesicles
  1. forebrain (prosencephalon)
  2. midbrain (mesencephalon)
  3. hindbrain (rhombencephalon)
• secondary vesicles form anteriorly by the time of posterior neural tube closure
  -the rhombencephalon is subdivided into rhombomeres, which represent distinct cellular territories with distinct neural fates
  -each rhombomere will form connections with rhomobomere derivatives that form ganglia, a cluster of neuronal cell bodies whose axons form a nerve; nerve identities will vary depending upon the rhombomere

Question 20

anterior neural tube forms three regions

Answer 20

-called primary vesicles
1. forebrain (prosencephalon)
2. midbrain (mesencephalon)
3. hindbrain (rhombencephalon)

Question 21

Hox gene

Answer 21

anterior/posterior patterning of the hindbrain and spinal cord is also controlled by Hox gene function

Question 22

patterning the neural tube along the D/V axis

Answer 22

• the nervous system is also patterned along the D/V axis
• in the spinal cord, this is reflected by differential function along this axis
• dorsal regions receive sensory input, while ventral regions contain motor neurons; communicating interneurons reside medially
  -differential and overlapping expression of transcription factors establish neural fates along the D/V axis

Question 23

Notochord Shh promotes neural tube floor plate

Answer 23

-experimental evidence indicates that Shh from the notochord induces ventral neural tube fate
-removal of notochord blocks floor plate development in the neural tube
-ectopic (abnormal) positioning of donor notochord laterally produces secondary floor plate cells
-similar ectopic placement of Shh is sufficient to reproduce floor plate fate

Question 24

Cell fates along the D/V axis are established by morphogen gradients

Answer 24

-early, the neural tube lies between the notochord and epidermis
-BMPs in the epidermis and Shh in the notochord induce regional expression of these signals in the neural tube itself (roof plate and floor plate)
-ventral shh and dorsal TGF-B signals create opposing gradients along the axis
-in combination, these gradients specify different D/V fates