Nervous System Development and Associated Disorders

Question 1

Describe gastrulation

Answer 1

• The process whereby the bilaminar embryonic disc undergoes reorganisation to form a trilaminar disc
• 2nd week - bilaminar embryonic disc contains epiblast and hypoblast
• Differentiates to form 3 germ layers, around 15 days after fertilisation. Begins with primitive streak formation. Forms a primitive node with a primitive pit, which expands to form a primitive groove
• Cells then move via the primitive groove in invagination, displacing the cells of the hypoblast
• This forms the definitive endoderm layer
• By day 16 the ectoderm is the most distal layer, and the mesoderm is formed between the endoderm and endoderm layer

Question 2

How does development prevent neurons fusing together?

Answer 2

• Neurons in development have growth cones, which contact each other via filopodia
• Repulsion: axons provide a repellent signal, altering the movement of the growth cone and ultimately the destination of the neuron

Question 3

Define induction

Answer 3

• A developmental mechanism:
• One tissue secrets signalling factors that instruct an abutting (neighbouring) tissue
  to differentiate to a new cell fate

Question 4

What is the role of the organiser

Answer 4

• Secretes neural inducing signals capable of organising the surrounding cells into brain and head
• Eg. Hensens node in chick, node and anterior primitive streak in mouse and most likely humans

Question 5

Where is the mamillian node

Answer 5

• Gastrulation front

Question 6

Describe the outcome of transplantation of the primitive node to another embryo

Answer 6

• Leads to a second body formation (anterior endoderm, node and node-derived notochord and prechordial plate arise here)

Question 7

Summarise brain development

Answer 7

• Brain forms on the “ectoderm” that consists of epiblast cells which do not ingress into the Primitive Streak (PS)

Brain is induced by signals emanating from tissues derived from the Anterior-PS (mammalian equivalent to Spemann Organiser):

• The Anterior Endoderm (AE) and
• The Node and the mesendoderm (notochord & prechordal plate)
• The AE signals are Antagonists of the signalling pathways: BMP, NODAL and WNT

Question 8

Where is the spinal cord derived?

Answer 8

From the primitive streak after node formation

Question 9

List signals required for spinal cord neuronal tissue

Answer 9

• FGF and WNT
• WNT and BMP
• Retinoic acid (spinal cord neural plate)

Question 10

Describe spinal cord development

Answer 10

• The primitive Streak (PS) generates Mesoderm and Endoderm, but recently it has been shown that the PS mesoderm behind the Node generates neuromesodermal (NMPs) precursors

Neuromesoderm gives rise to

• the somites: two rows of condensed structures, which are separated by the node-derived mesendoderm and
• the neural tissue (neural plate) above the somites that will form the spinal cord neural plate
• WNT and FGF Signals together generate NMPs
• Then FGF alone differentiate NMPs to neuronal precursors; then + Retinoic Acid => spinal cord
• While WNT alone convert the NMPs to somites

Question 11

Where does the PNS develop from?

Answer 11

Neural crest cells derived from the roof plate

Question 12

Why do we study development

Answer 12

• To learn the underlying causes of diseases
• Regenerative medicine to use human ESC and iPSC to study human development, develop therapies and derive specific tissues in cultures and use them for cell replacement therapies

Question 13

What happens without the organiser?

Answer 13

Spinal cord but no brain

Question 14

What causes holoprosencephaly

Answer 14

Defects in the mesendoderm

Question 15

Define patterning

Answer 15

• A developmental mechanism where naive cells position determines the amount of signal that it receives.
• Each level of the signal is interpreted by the naive cell into different cell fate, therefore each cell fate develops at a different position within the gradient.