L3 - Formation of Neural Plate Flashcards
Formation of neural precursors
Neural precursors first form at the surface
They develop next to the future skin on one side and next to mesoderm on the other side
Homologous genes
Have different names in vertebrates and insects
- BMP7/Screw
- BMP1/Toll
- BMP4/DPP
- Chordin/SOG
Chordin/SOG
Inhibit BMP signalling
How does he neurogenic region arise overview
BMP/DPP signalling inhibited by antagonists
BMP and chordin are proteins encoded by genes conserved across evolution
The DPP/SOG network broadly dictates dorsal and ventral sides
BMP/DPP signalling inhibited by antagonists
Chordin/SOG - act as sponges for BMP/DPP
BMP and chordin are proteins encoded by genes conserved across evolution
BMP binds to receptor which leads to phosphorylation of SMAD
SMAD enters nucleus and acts within transcription factor complex
DPP/SOG network broadly dictates dorsal and ventral sides
DPP – dorsal
SOG – ventral
Evo-Devp
Suggests dorsal versus ventral nervous system
Developed as invertebrates underwent a body twist
So similarly, but reverse orientation, the neural plate forms where chordin inhibits BMPS
Molecular pathway for development of neural plate cell
- BMP
- Low Smad1 and high Smad7
- Neutralising transcription factors
- Neurogenin
- NeuroD
- Neural differentiation
What is neurulation?
As vertebrate development progresses the neural plate rolls up to form the neural tube
What is spina bifida?
Often have opening of the neural tube in the lower back
In the Xenopus following fertilisation…
The egg undergoes mitotic cleavages and gives rise to hollow ball of cells
- 3 germ layers will form
Mesoderm development in the Xenopus
Specialised type of mesodermal cell is induced – organiser
- Known as node in chicks and humans
It expresses special transcription factors and secreted ligands
Under the influence of transcription factors, the organiser expresses secreted products that are antagonists of BMP signal
- Chordin, Noggin, Follistation, Gsc
Neural plate induction
It is induced in ectoderm where BMP is inhibited
BMP antagonists prevent the BMP ligand from stimulating its TGFβ receptors
Differences between chick and human development
Flat not curved
Node secretes BMP antagonists which induce the neural plate
- Found in horse-shoe shape around node which extend downwards forming the neural plate
Node found at the end of the primitive streak
- BMP antagonists can be detected by in situ hybridisation with antisense probe
What is gastrulation?
Development of axial mesendoderm (anterior endoderm/prechordal mesoderm/notochord) drives elongation and transition to neural tube
Cells in the organiser differentiate into anterior endoderm and axial mesoderm
Invagination
Sheet of cells bends inwards
Ingression
Individual cells leave epithelial sheet becoming free migrating mesenchyme cells
Involution
An epithelial sheet rolls inward to form an underlying layer
Epiboly
Sheet of cells spreads by thinning
Intercalation
Rows of cells move between one another, creating longer but thinner sheet
Convergent extension
Rows of cells intercalate but the intercalation is highly directional
During gastrulation the anterior end/prechordal mesoderm are in close contact with?
The pharynx and ventral forebrain
Experimental proof for neural induction by organiser
Took organiser from donor newt and transplanted to opposite side on host newt
BMP antagonists from grafted region diffuse out and induce to a neural identity
Leads to development of a second neural tube
Discovery of BMP antagonists
- Extract all mRNA from organiser cells
- Reverse transcribe to cDNA
- Test each to look for gene/protein that mimics organisers ability to induce secondary neural plate
Features of neural inducers in organiser
Must be expressed in organiser
Must be secreted and act on adjacent cells
Overexpression in an ectopic site should lead to induction of secondary axis
Inhibition of activity should prevent axis formation
- Knock out
- Injection of dominant negative effector of signalling pathway
Show BMP antagonism is necessary for neural induction
