Developmental Neurobiology Flashcards
steps to establish a neurone
- cellular determination
- proliferation
- cell migration
- axon projects out
- axon connections to target form
- prune unnecessary connections
- death of excess neurones
briefly describe development
- fertilisation
- divisions to form 8 cells
- blastula forms (ring of cells around blastocoele)
- gastrula forms by invagination
(forms the 3 germ layers)
determination
ectoderm cells determined to become neurones by neural induction
-> neural inducer signals from mesoderm
after determination
EITHER
differentiate into neurones
OR
remain as neural precursors
what do neural precursors become?
neurones
OR
glial cells
what happens to the ectoderm in an embryo (during development)?
inhibition process prevents cells becoming neurones
- must be switched off for differentiation
organogenesis
- define
= different germ layers become rudimentary organs
via folding, splitting + dense clustering of embryo
organogenesis
- 1st rudimentary NS organs
- how do they form?
neural tube
neural crest
neurulation
= neural plate folds inwards to form neural tube
the notochord helps to induce the floor plate
as neural tube forms neural crest cells immigrate from dorsal aspect of tube
Xenopus laevis
- experiments
animal cap (ectoderm) transplanted onto second embryo -> grew second NS
Spemann organiser (mesoderm)
transplanted
-> forms nervous tissue
Xenopus laevis
- Spemann organiser
contains cells releasing neural inducers
e.g. Noggin, Chordin, Follistatin + Cerebrus
fertilisation
polarises egg
- animal and vegetal poles
influx of Ca2+ in vegetal pole
- > diffuses across egg
- > rapid release of cortical granules
- > forms fertilisation envelope
- > blocks polyspermy
cortical rotation
- what happens
- what does it form
egg membrane rotates in relation to molecules within egg
- > mixes cytoplasmic determinants
- > creates dorsal-ventral axis
sperm point of entry determines ventral (entry point) and dorsal (opposite entry)
cortical rotation
- redistributes maternal cytosolic determinants
VegT associated with Disheveled at membrane
- > cortical rotation separates
- > Dsh interacts with Siamois
Nieuwkoop Centre forms at area of separation
fate mapping the blastula
- axes formed by?
- name axes
- what induces them
gradients of signalling molecules
animal-vegetal
(maternal determinants)
dorsal-ventral
(sperm entry + cortical rotation)
anterior-posterior
(Spemann organiser)
organiser transplant experiment
- what happens
- what does this show
region above blastopore lip transplanted to ventral side of host from EARLY gastrula
-> develops secondary dorsal axis
(evident by secondary neural plate)
this region containing Spemann Organiser is important for inducing NS formation
what do neural crest cells form?
PNS
endocrine cells
connective tissue
neural tube structure
top (anterior)
- brain
bottom (posterior)
- spinal cord
ventricular zone of proliferation
area within neural tube
gives rise to all neural cells
Smad pathway
Bone morphogenic proteins
= neural inhibitors
Ectoderm cells have BMP receptors
- BMP binding -> phosphorylation of Smad-1
- > activate Smad-1 binds to Smad-4
- > changes TF expression
- > inhibits expression of neural genes + activates epidermal genes
- > induces ectoderm to become epidermis
how do neural inducers affect the Smad pathway?
neural precursors express inhibitory protein
- > binds to neural inducers
- > inhibit BMP binding to receptors and Smad pathway
proliferation
division of precursors during and after differentiation
-> ends in neuroblasts (these migrate)
results in excess cells in adult NS
- > not fully determined cells become stem cells
- > can form progenitor cells
- > eventually form neuroblasts
neural stem cells
- 2 properties
- rare set of cells in brain tissue
self-renewing
multipotent
single cells divide into neurospheres
-> differentiate into neurones, astrocytes + oligodendrocytes
neural stem cell transplants
human NSCs transplanted into rat brain:
some differentiate into neurones
-> migrate into brain regions
have appropriate morphology for brain region
incorporated into circuits
neuronal tube generates different neuronal and glial cell types
- where do they arise?
- cerebral cortex cells
arise from ventricular proliferative zone (VPZ) in neuronal tube
migrate to final position along elongated radial glial cells
- early neurones migrate to close sites, later ones to far locations
cerebral cortex
- how many layers?
- how do they develop?
6 layers of neurones
early differentiated cells move to lower regions
later differentiated migrate to top of cortex
radial glia
span from VPZ to outer surface of neural tube
migrating precursors travel along the axons to final location
how to determine birth dates of neurones in a monkey
- inject radioactive thymidine in short pulse
- only cells in S-phase incorporate it into DNA
- cells that make terminal division heavily labelled
- cells that continue to cycle dilute label
- pulse label at various times during development + section brain after birth
molecular gradients
- anterior-posterior
proteins such as Noggin + Chordin are essential for formation of anterior parts of brain
FGFs
Hox genes
molecular gradients
- dorsal-ventral
sonic hedgehog
- secreted from notochord
Wnt and BMP
- secreted from ectoderm
signalling molecule gradient in neural plate
high Wnt, FGFs + RA at posterior end
–> lower at anterior end
leads to different structures forming
signalling molecule gradient
- dorsal-ventral axis
notochord (ventral) releases sonic hedgehog
- diffuses into neural tube
= forms gradient
-> influences transcription factors and the proteins expressed
-> affects fate of neurones
dorsal side of tube affected more by proteins secreted by ectoderm
sonic hedgehog
binds to 2-part receptor
(smoothened and patched)
alters gene transcription
cell-cell interactions
- lateral inhibition in nervous system
notch protein expressed on 1 cell type and delta expressed on another
- > interact
- > creates inhibitory signal into cell
- > inhibition
- > prevents ectoderm cells differentiating into neuroblasts
what can this form of lateral inhibition do in vertebrate nervous systems?
stimulate differentiation of neuronal precursors into special cell types
e.g. photoreceptors
