9. Neural Development Flashcards
where does neural stem cell replication occur
in the ventricular zone of the neural tube
for a neuroepithelial cell to produce radial glia, what genes must it be under the influence of
either:
FOXG1
HX2
PAX6
what are radial glia used for
neuronal migration
where does the neural tube begin closing up
in the middle (think of it like a burrito)
what are the openings of the neural tube called
anterior and posterior neuropores
which neuropore of the neural tube closes up first
the anterior neuropore closes on day 25
the posterior neuropore closes on day 27
what are somites
bilaterally paired blocks of mesoderm that form along the head-to-tail axis
what signalling molecule determines the anterior-posterior axis
Wnt
what is Wnt signalling role in the dorsal-ventral axis
Wnt specifies the Nieuwkoop centre by allowing beta-catenin release and translocation
name 3 Wnt inhibitors
dickkopf
cerberus
insulin-like growth factor
what are Wnt inhibitors also known as
paracrine factor antagonists
what produces Wnt inhibitors, why?
the organiser and dorsal anterior mesoderm
this allows neuroectodermal tissue to be established
what is the evidence for the role of Cerberus in allowing neuroectoderm development
ectopic placement of Cerberus during early gastrulation produces a secondary head structure
where is Wnt found in high concentrations
the ventral, posterior aspect
what 2 molecules are important in anterior-posterior patterning
fibroblast growth factor (FGF)
retinoid acid
where is fibroblast growth factor found in high concentrations
in the posterior end
(it is degraded at the anterior)
where is retinoic acid found in high concentrations
high concentrations in the middle of the embryo
where is retinoid acid made
by the central mesoderm
what do FGF, RA and Wnt signalling all regulate
Hox gene expression - these genes act as positional cues
what two gradients control torso-ventral patterning
Wnt and TGF-beta
describe what happens to dorsal neurons of the spinal cord
high Wnt signalling instructs them to become sensory neurons
describe what happens to ventral neurons of the spinal cord
low concentrations of Wnt signal to them to become motor neurons
what happens to the anterior part of the neural tube in the first stages of brain development
the anterior part divides to form three primary vesicles:
the forebrain, midbrain and hindbrain
what happens to the forebrain? what does it go on to form?
it curls up to form a three pronged structure that develops into the cerebral cortex
what happens to the posterior part of the neural tube
it forms the spinal cord
what does the midbrain go on to form
vision, hearing and motor control
what does the hindbrain go on to form
the medulla, pons and cerebellum
how many layers is there in the cerebral cortex
6
what is the internal and external layer of the cerebral cortex
the external layer is the molecular layer
the internal layer is the fusiform layer
describe pyramidal neurons
cell body is a triangular shape
they have extensive up reaching dendrites
typically glutamatergic neurons
describe the movement of the first cohort of post-mitotic neurons
moves up from the ventricular zone towards the pial surface to form the preplate
how do post-mitotic neurons get transported
across the radial glial cell scaffold
the first wave of neurons arrive in the prelate, what then happens?
the prelate is split into three zones:
1. marginal zone
2. cortical plate
3. subplate
what do neural stem cells produce
nestin
cortical plate neurons arrive in an inside out sequence, what does this mean?
the earliest born neurons become layer 6
and the last to arrive become layer 2
how can we visualise neural stem cells
using an anti-nestin antibody
what type of protein is nestin
an intermediate filament protein
what do immature glial cells (including radial glial cells) produce
vimentin
how can we visualise radial glial fibres
using aan anti-vimentin antibody
how do neurons migrate towards the target area
they detach from radial glia and can translocate tangentially to their final position
what is reelin
an extracellular matrix-associated glycoprotein
what type of cells secrete reelin
cajal-retzius cells
where are cajal-retzius cells found
in the marginal zone
where is reelin secreted by the cajal-retzius cells
cajal-retzius cells have ascending processes which contact the pial surface and secrete reelin
name 2 receptors reelin binds to
very low density lipoprotein receptor (VLDL-R)
apolipoprotein E receptor type 2 (ApoER2)
what happens once reelin binds to the receptor
disabled 1 binds to the cytoplasmic tail of the receptor and gets phosphorylated
downstream kinase signalling results in gene expression that drives migratory behaviour
what happens in reeler and scrambler mice
the preplate fails to split because new neurons are unable to penetrate into it
what are reeler and scrambler mice
mice that are null for reelin and disabled 1
what is human reelin mutation linked to
lissencephaly and autism
how can you visualise preplate neurons
staining with chondroitin sulphate proteoglycans
some stem cells are retained in the human brain, give 2 examples
dentate gyrus stem cells involved in memory
doublecortin - expressed by immature neurons
what part of disabled 1 becomes phosphorylated
the phosphotyrosine interacting domain
after Dab1 is phosphorylated, what can it now do
bind to protein tyrosine kinases Src, Abl and Fyn
what happens in mutations of the doublecortin gene
defective migration of neurons results in poorly organised layers of the cortex
= double cortex syndrome or lissencephaly dependent on gender
why does the pathology associated with doublecortin mutations depend on gender
DCX gene is located on the X chromosome, so females have half a functional copy of the gene that results in half the cells migrating correctly, the others do not
= double cortex syndrome
no functional copy of the DCX protein = lissencephaly
how is doublecortin implicated in cancer metastasis
unstable interaction between DCX and microtubules destabilises the cellular organisation = disorganised cell movement
what is doublecortin
a microtubule associated protein
where is doublecortin expressed
in migrating neurons of the CNS and PNS during embryonic and postnatal development
why do neural crest cells become peripheral neurons and ganglia
because they have a low affinity for neurotrophic p75 receptor
what produces radial glia progenitor cells
neuroepithelial stem cells
where do neural stem cells develop from
the ventricular zone of the neural tube
name 3 things neural stem cells go on to produce, which first
neurons
astrocytes
oligodendrocytes
what is the role of SOX2
what happens if there is a loss of SOX2
maintaining neural stem cells
loss of SOX2 = causes the cell to exit the cell cycle
what is the role of SOX1 and SOX3
regulate neural progenitor cell states
why is there not many stem cells in the adult brain
