Lecture 5: Development of the nervous system Flashcards
What are the integrated steps required for the construction of the nervous system?
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
What is the entire CNS formed from?
the neural plate
What is epidermal fate determined by?
local bone morphogenic protein (BMP) signalling
How is neural fate induced?
signals from “organiser” region block the BMP signal inducing neural fate
What happens during neural induction?
a region of the dorsal embryonic ectoderm acquires neural fate which is the potential to form the nervous system
What happens during neurulation?
formation of the neural tube
What are the steps of neurulation?
elevation of neural folds -> neural folds fuse in dorsal midline -> neural tube pinched off from epidermis
What causes neural tube defects?
failures in neural tube closure
What are examples of neural tube defects?
the neural tube “zips up” bidirectionally from initial points of closure
neural tube defects caused by failure of neural fold formation or closure
What do cells at the neural plate margin differentiate into?
neural crest cells
What happens when the dorsal margins of the neural tube fuse?
the neural crest cells migrate from this region
What does the neural crest give rise to?
peripheral and enteric NS ganglia, melanocytes, Schwann cells, cartilage and bone (face, jaw)
What happens following neural tube closure?
primary and secondary brain vesicles from:
- > wall: neuroepithelium
- > fluid-filled central cavity: ventricular system
Which three distinct vesicles form at the rostral end of the neural tube?
prosencephalon (forebrain)
mesencephalon (midbrain)
rhombencephalon (hindbrain)
What does the prosencephalon split into and what does the rhombencephalon split into?
prosencephalon -> telencephalon and diencephalon
rhombencephalon -> metencephalon and myelencephalon
How is the patterning of the neural tube established?
gradients of morphogens from patterning centres or organising regions provides different positional cues for specifying cell fate
How does the overlying ectoderm induce the roof plate?
secretes dorsalising morphogens (BMPs, FGF, Wnts)
How does the underlying notochord induce the floor plate?
secretes ventralising morphogen
What do the brain vesicles / neural tube initially consist of? Why do these structures appear to be multi-layered?
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
What is the role of symmetric divisions?
expanding the NE progenitor pool (early) or giving rise to two neurons (late)
produce two identical daughter cells
What is the role of asymmetric divisions?
radial glia divide and produce i) another RG (self-renew) and ii) a differentiated neuron
produce two different daughter cells
What do radial glia provide a scaffold for?
radial migration of their post-mitotic neuron progeny
What do the earliest neurons to be “born” form?
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
In which type of sequence do neurons of the cortical plate assemble into?
an “inside-out” sequence: the deepest cellular layers are assembled first and those closest to the surface last
What is a common theme of neuronal development?
neurons are generated at remote locations and need to migrate into place
What is the production of neurons and glia controlled by?
separate transcriptional programs, each blocks the other
How does information flow through neurons?
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
What do neurons in the mature cortex exhibit?
great morphological and functional diversity
What are pyramidal neurons in the mature cortex?
excitatory long-range projection neurons -> axons project to other cortical hemisphere or subcortical targets like spinal cord
What are interneurons in the mature cortex? What do they modulate?
locally-projecting inhibitory neurons that modulate cortical excitatory output
What is growth and branching of dendrites influenced by?
environmental factors:
- > local signals (contact-dependent or diffusible cues)
- > active synapses
Where does axon growth take place?
at the highly motile tip of the neurite, the growth cone
What is the role of actin filaments?
regulate shape and directed growth of the growth cone (extension, retraction)
What is the role of microtubules?
they provide structural support to the axon shaft and are essential for axon extension
What does the growth cone sense and integrate?
all the attractive and repulsive signals
How does excitatory synapse density change in the early post-natal years? Where does synapse density form?
increases dramatically
on dendritic spines
How is synaptic connectivity refined?
connections initially overproduced
performance improved by adjusting number, boundaries, strength of connections through a competitive process
