Lecture 5: Development of the nervous system

Question 1

What are the integrated steps required for the construction of the nervous system?

Answer 1

neural induction, neurulation, morphogenesis and patterning of neural tube, neurogenesis, neuronal migration, axon growth and pathfinding to find appropriate targets and dendritic arborization, synaptogenesis and gliogenesis / myelination

Question 2

What is the entire CNS formed from?

Answer 2

the neural plate

Question 3

What is epidermal fate determined by?

Answer 3

local bone morphogenic protein (BMP) signalling

Question 4

How is neural fate induced?

Answer 4

signals from “organiser” region block the BMP signal inducing neural fate

Question 5

What happens during neural induction?

Answer 5

a region of the dorsal embryonic ectoderm acquires neural fate which is the potential to form the nervous system

Question 6

What happens during neurulation?

Answer 6

formation of the neural tube

Question 7

What are the steps of neurulation?

Answer 7

elevation of neural folds -> neural folds fuse in dorsal midline -> neural tube pinched off from epidermis

Question 8

What causes neural tube defects?

Answer 8

failures in neural tube closure

Question 9

What are examples of neural tube defects?

Answer 9

the neural tube “zips up” bidirectionally from initial points of closure
neural tube defects caused by failure of neural fold formation or closure

Question 10

What do cells at the neural plate margin differentiate into?

Answer 10

neural crest cells

Question 11

What happens when the dorsal margins of the neural tube fuse?

Answer 11

the neural crest cells migrate from this region

Question 12

What does the neural crest give rise to?

Answer 12

peripheral and enteric NS ganglia, melanocytes, Schwann cells, cartilage and bone (face, jaw)

Question 13

What happens following neural tube closure?

Answer 13

primary and secondary brain vesicles from:

• > wall: neuroepithelium
• > fluid-filled central cavity: ventricular system

Question 14

Which three distinct vesicles form at the rostral end of the neural tube?

Answer 14

prosencephalon (forebrain)
mesencephalon (midbrain)
rhombencephalon (hindbrain)

Question 15

What does the prosencephalon split into and what does the rhombencephalon split into?

Answer 15

prosencephalon -> telencephalon and diencephalon

rhombencephalon -> metencephalon and myelencephalon

Question 16

How is the patterning of the neural tube established?

Answer 16

gradients of morphogens from patterning centres or organising regions provides different positional cues for specifying cell fate

Question 17

How does the overlying ectoderm induce the roof plate?

Answer 17

secretes dorsalising morphogens (BMPs, FGF, Wnts)

Question 18

How does the underlying notochord induce the floor plate?

Answer 18

secretes ventralising morphogen

Question 19

What do the brain vesicles / neural tube initially consist of? Why do these structures appear to be multi-layered?

Answer 19

a single layer of neuroepithelial cells
appears multi-layered because the nucleus and cell body move to different positions along the apical-basal axis with different phases of the cell cycle

Question 20

What is the role of symmetric divisions?

Answer 20

expanding the NE progenitor pool (early) or giving rise to two neurons (late)
produce two identical daughter cells

Question 21

What is the role of asymmetric divisions?

Answer 21

radial glia divide and produce i) another RG (self-renew) and ii) a differentiated neuron
produce two different daughter cells

Question 22

What do radial glia provide a scaffold for?

Answer 22

radial migration of their post-mitotic neuron progeny

Question 23

What do the earliest neurons to be “born” form?

Answer 23

undergo terminal division and form the preplate which is split into the marginal zone and the suplate as the first wave of cortical plate neurons arrive

Question 24

In which type of sequence do neurons of the cortical plate assemble into?

Answer 24

an “inside-out” sequence: the deepest cellular layers are assembled first and those closest to the surface last

Question 25

What is a common theme of neuronal development?

Answer 25

neurons are generated at remote locations and need to migrate into place

Question 26

What is the production of neurons and glia controlled by?

Answer 26

separate transcriptional programs, each blocks the other

Question 27

How does information flow through neurons?

Answer 27

dendrites: collect electrical signals
cell body: integrates incoming signals and generates outgoing signal to axon
axon: passes electrical signals to dendrites of another cell or to an effector cell

Question 28

What do neurons in the mature cortex exhibit?

Answer 28

great morphological and functional diversity

Question 29

What are pyramidal neurons in the mature cortex?

Answer 29

excitatory long-range projection neurons -> axons project to other cortical hemisphere or subcortical targets like spinal cord

Question 30

What are interneurons in the mature cortex? What do they modulate?

Answer 30

locally-projecting inhibitory neurons that modulate cortical excitatory output

Question 31

What is growth and branching of dendrites influenced by?

Answer 31

environmental factors:

• > local signals (contact-dependent or diffusible cues)
• > active synapses

Question 32

Where does axon growth take place?

Answer 32

at the highly motile tip of the neurite, the growth cone

Question 33

What is the role of actin filaments?

Answer 33

regulate shape and directed growth of the growth cone (extension, retraction)

Question 34

What is the role of microtubules?

Answer 34

they provide structural support to the axon shaft and are essential for axon extension

Question 35

What does the growth cone sense and integrate?

Answer 35

all the attractive and repulsive signals

Question 36

How does excitatory synapse density change in the early post-natal years? Where does synapse density form?

Answer 36

increases dramatically

on dendritic spines

Question 37

How is synaptic connectivity refined?

Answer 37

connections initially overproduced

performance improved by adjusting number, boundaries, strength of connections through a competitive process