neural development 1 Flashcards
at blastocyst stage what do primate embryos show
trophectoderm and inner cell mass
on post-implantation day 10 what do rhesus macaque embryos show
the developing of the the amion through cavitation of inner cell mass with the trophectoderm and extra-embryonic endoderm
what happens at human day 9
10.5
11.5
and 13
9 - extension of the extra-embryonic endoderm around the blastocoel cavity
10.5 - characteristic mesh of extra-embryonic endoderm with the blastocoel cavity
11.5 - extra-embryonic mesoderm
13 - rhesus macaque embryo - externsion of the primitive streak from caudal epiblast, subsequent to extensive development of the extra-embryonic mesoderm, has a secondary yolk sac
what is the inner cell mass
a group of cells which are stem cells
what does the epiblast emerge to
an epiblast sheet, as the sheet develops so does the neural form
what happens at the neural plates stage in human embryp
primitive streak is in the future spinal chord
top part is the organiser which sends out signals to change external surroundings
how does neural development begin
with neural plate induction
movement of the organiser reorganises tissue
the organiser is a source of tissues that can direct the neural plate
how do signals that inhibit bone morphogenetic protein (BMP) mimic the organiser and promote formation of the neural plate
when BMP is expressed throughout the xenopus blastula, the neural plate form from the prospective ectoderm when BMP signalling is inhibited by antagonists from the organiser
how has bmp activity lead to the default model of neural induction
BMP antagonising activity from the organiser has lead to the formulation of the default model for neural induction
from ectoderm cells will form neural tissue unless they receive signals that induce epidermal differentiation - so the default state is the neural state
so neural induction requires signals that inhibit the epidermal inducer BMP$
BMP antagonists in the organiser include Noggin and Chordin
the organiser secretes the BMP antagonists
how do factors that stimulate MAPK pathway promote neural cell fate
they interfere with BMP signal transduction
FGF-MAPK signalling contributes to neural induction
MAPK inhibition of smad1 activity, an intermediate in the BMP signalling pathway that would otherwise translocate to the nucleus to activate BMP target genes
FDF, IGF and HGF can also stimulate this
how does the CNS develop from distinct anterior-posterior regions
anrerior mesoderm induces forebrain
posterior mesoderm induces spinal chord
if neurula anterior mesoderm is grafted into early gastrula and induces and extra head with eyes and forebrain
if neurula posterior mesoderm is grafted into early gastrula it gives a trunk and tail
how is the nerual tube formed
the neural plate roles up
called neurulation
neural crest ells form the dorsal neural tube and give rise to the PNS including glangia in head and gut
future motor neurones and associated interneurons are locarted ventrally and form the ventral root sin the spinal chord
commissural neurons are secondary and their associated inter-neurones differentiate primarily in the dorsal region
spinal chord extends their axons on the side the originated
what do primary sensory neurones develop from
the neural crest cells located laterally and dorsally in the neural tube
what is the floor and roof plate
a group of non neural cells in the ventral midline of the neural tube
the roof plate is non neural cells in the dorsal midline
the floor and roof plates produce signals that pattern the neural tube along its dorso-verntal axis
the floor plate is induced by signals secreted by the mesodermal notochord immediately below the neural tube
what happens if the notochord is grafted to another area
patterning can be seen, it induces a second floor plate
what induces floor plate cells to produce Shh
sonic hedge hog, this then forms a gradient of activity from ventral to dorsal in the neural tube and acts as the ventral patterning signal
what is commitment to the motor neurone progenitor cells from the neural tube driven by
Shh from the floor plate by retinoic acid secreted by the adjacent mesoderm
how does progressive subdivision help regionalisation of the CNS
the isthmus, separating the midbrain and hindbrain
regionalisation of the CNS is progressive and cell to cell signalling plays an important role in this
local organising centres within the brain such as the isthmus is located at the midbrain to hind brain border to help subdivide neural tissue into regions and functionally distinct cell populations
how do grafting experiments demonstrate patterning properties of the isthmus
grafting isthmus converts anterior midbrain to posterior midbrain
grafting the isthmus to the posterior hind brain converts this to anterior hindbrain
patterning mid and hind brain - FGF signalling induces r1 gene, engrailed 2 in move posterior hindbrain
isthmus patterns tissues via FGF/Wnt signalling
hind brain is divided into sections called rhombomeres which have distinct molecular identities
hox genes provide a combinatorial code that distinguishes rhombomeres
what are hox genes
transcription factors
conserved across species and are an ancient means to convey personal identity
the order they are in on the chromosome is the same order they are expressed in
they code for specific identities
what happens when hoxb1 is lost
it converts rhombomere 4 to rhombomere 2
altering expression of hox genes least to homeotic transformations
distinct hox gene combinations define different antero-posterior regions of the body axis including the spinal chord
retinioc acid provided by somites promotes anterior hox genes
how does the retinoic signalling pathway work
retinoic acid is derived from vitamin a
lack of and excess of retinoic acid leads to developmental defects
in chicken eggs and mammalian embyro retinol is supplied by maternal circulation
retinol binds to retinol binding proteins in extracellular space and is transported into cells by rhe transport receptor
retinol binds to CRBP and produces retinoic acid in a 2 step reaction
retinol is first metabolised by retinaldehyde by retinol dehydrogenases or alcohol dehydrogenases
retinaldehyde is then metabolised to retinoic acid by retinaldehyde dehydrogenases
activation - transformation hypothesis
- induce anterior neural gene= inhibition of BMP signalling
- experience posteriorising factors = retinioc acid, FGF and Wnt signalling
the neural tube is induced with anterior character and is trnasformer or posteriorised
further subdivisions of nervous systems take place as development proceeds
how is caudal most neural tissues generated in chick and mice
from a stem zone in the tail bud
cells in the stemzone imclude neuro-mesodermal projenisotrs which contribute to both spinal chord and paraxial mesoderm as the body axis elongates
nmps are induced and maintained by fgf and wnt signalling which also promotes expression on caudal (5’0 how genes
what are the specific positions of distinct cell types in the neural tube
the nervous system consists of neurones and supporting cells
neurons are first born in the neural tube
diff types of neurons form in diff and specific areas of the tube
specialised non neural cells are also present
how do signals from the notochord pattern the neural tube
notochord signals are needed to induce the floor and roof plates
protein Shh is expressed by notochord and floor plate
failure to express Shh leads to abcense of the ventral midline
Shh specifies ventral cell types, diff concs specify diff types of ventral neuron
Shh controls a combinatory code of transcription factors that deterimine neuronal cell type
opposing gradients of dorsal tgfb and ventral Shh signalling specify cell types in the neural tube
