early development of the nervous system Flashcards
what are the 3 layers formed during gastrulation?
ectoderm, mesoderm, endoderm
when does gasturalation start and when does neurulation occur?
@7 days
neurulation occurs at the same time as gastrulation
what is the primitive streak?
it defines the midline ( starts in the posterior and proceeds anteriorly
what happens by the end of gastrulation?
the midline of of the embryo is defined by the formation of the notochord.
this is critical for the formation of all tissue including the CNS.
what is the first event in neurogensis?
the formation of neural ectoderm which is induced by the defined midline ( notochord formation)
what is the notochord formed of?
mesoderm and is a transient structure which is completely replaced by the neuroplate in humans
if ectoderm is exposed to bone morphogenic proteins (BMPs) then they become___________
epidermis
if ectoderm exposed to noggin/chordin (( and follistatin) all produced in the notochord) then it becomes____________
neuroectoderm
noggin and chordin inhibit_____________
bone morphogenic proteins (BMPs)
thus in the absence of BMPs ectodermal precursor cells will become neurons
bone morphogenic proteins (BMPs) come from ?
mesoderm
BM binds to ____________ and ___________ that is transported to the nucleus to mediate transcription.
receptor kinases and a SMAD complex
Besides inhibition of BMP, inhibition of what other signaling promotes stem cell commitment to neural cells?
inhibition of:
- Nodal signaling
- Wnt signaling
stimulation of ________,____________, and ___________ induce neural stem cell formation
retinoid acid (RA)
fibroblast growth factor (FGF)
insulin-like growth factor (IGF)
why is it that when separated ( a petri dish for e.g.) from the other layers ( mess and endo -derm) does ectoderm form neurons but when intact it forms epidermis?
because BMPs needed to form epidermis comes from mesoderm.
what does fibroblast growth factor (FGF) do?
it stimulates production of nogin which in turn inhibits BMP and leads to neural induction.
what cells make up the neural tube?
neural stem cells
after neural induction what happens to the neural plate?
the lateral margins of the neural plate fold inward to form the neural tube.
the floor plate and roof plate of the neural tube are key for_______
signaling
the central nervous system is a ( think shape)____________
a tube
_____________, particularly _____________ is important for the closure of the neural tube.
b-complex vitamins, especially folic acid
what is anencephaly?
lack of fore brain
what does the neural crest give rise to?
peripheral nervous system, cartilage, bone, connective tissue, pigment cells, and sympathy-adrenal cells
what are some neural tube closure defect?
spina bifida ( most common)- failure of posterior end of the neural tube to close
anacephaly and holoprosencephaly ( both typically deadly)
formation of the neural plate and neural groove are _________dependent
sonic hedgehog dependent
sonic hedgehog is expressed____________
is expressed only in the notochord and fore plate
the ventral signal ( motor) is?
sonic hedgehog (Shh)
the dorsal signal ( sensory) is?
TGF betas ( mainly BMP)
Sonic Hedgehog absence in the roof plate produces _______
dorsal-ventral polarity ) see pg 42
describe Sonic hedgehog signaling (Shh)
Shh binds to patched protein which relieves Patched protein dependent inhibition of smoothened thus changes the identity of the cell (cell fate).
what does smoothened do?
smoothened activates the Gii class zinc finger transcription factors
what does Gli do?
Gli induces transcription and leads to a ventral (motor neuron) cell fates.
what can absence of Shh result in?
holoprosencephaly - forebrain does not form and Dorsal ventral pattern is disrupted.
cancers like: medulloblastomas, and basal cell carcinoma
cyclopia- one eye ( seen in humans and in sheep ( sheep ate cyclopamine and Shh antagonist))
what does Shh regulate?
polarity and proliferation
in addition to BMPs and Shh pathways ______ and _________play a key role in dorsal ventral pattenrning
retionic acid ( RA) and fibroblastic growth factor (FGF)
what are Hox genes?
transcription factors critical for body plan ( patterning): really only for the hindbrain, research is going on to figure out what goes on in the forebrain
what is symmetric differentiation?
differentiation into 2 neurons or 2 neuronal stem cells
what is asymmetric differentiation?
differentiation into a neuron and a different neuronal stem cell
where do nerve stem cells proliferate and differentiate?
in the ventricular zone ( which surrounds the CSF-filled ventricles)
inhibition of notch gives rise to?
neurons
what cells have a lot of notch?
neurostem cells which inhibits pro neural genes and keeps it in a pleuripotent state and down regulates delta
what do pro neural genes do?
they inhibit differentiation of glia
why does the brain get bigger after birth?
brain gets bigger because of continuing connections made after birth and myelination
what does anterior posterior patterning lead to?
spinal cord, rhombencephalon ( future pons and medulla), mesencephalon- future midbrain, prosencephalon ( future thalamus and retina, and future forebrain
how do hox genes work?
by repressing and enhancing each other to create unique patterns of gene expression in each segment
neural progenitors give rise to?
neurons and glia
in early development how to neural stem cells divide?
symmetrically
as development continues how doe neural stem cells divide ?
asymmetrically
late in development how do neural stem cells divide?
symmetrically but giving rise toe 2 neural precursors thus neural stem cells disappear
how do neural precursor cells divide?
symmetrically and asymmetrically
neurogensis proceeds ____________
gliogenesis
vitamin A excess or to little vitamin A, or drug abuse lead to?
birth (neural) defects
cells made earlier are closer to the ________ and cells made later are closer to the ______
ventricular surface
pial surface
where are projection neurons made?
the ventricular zone
what is lissencephaly?
failure of gyri ( or fold ) formation
where are interneurons made?
in the lateral or medial ganglionic eminence along the ventricular zone
what path do interneurons take?
the tangential path for migration through the CSF. they migrate based on where the projection neurons went.
when does neurogenesis in humans end?
by the end of the middle of the second trimester ( 19 weeks)
when does gliogenesis end in humans?
sometime after birth ( to about 20 years old)
when is primary neurulation complete?
within the first 3 weeks of pregnancy
how does the cortex form?
in an inside out manner the first layer formed is closest to the ventricular zone
what do radial gill cells do?
they rise to neurons and provide scaffolding on which they can migrate to their appropriate destination ( see pg 68)
what does a mutation in the extracellular matrix protein reel in do?
results in a disruption of radial migration and causes earliest neurons to be on the outer surface rather than the inner surface near the ventricular zone.
what are Mash1 and DLX1 and DLX2 involved in?
interneuron tangential migration
describe how notch and Bhlh signaling resulate neural stem cell differentiation
see board (fill in later)
