Anterior vs posterior Flashcards
What are the anterior fates of the embryo?
The forebrain
What are the posterior fates of the embryo?
The hindbrain and spinal chord
What 3 components is the nervous system made of?
1) CNS
2) PNS
3) Enteric nervous system
What is the CNS comprised of?
- Brain
- Spinal chord
- Specialised sensory derivatives derived from forebrain tissue (eg. retina, olfactory, taste receptors)
Where are all the components of the nervous system derived from?
From the neural plate of the line of cells which lie on the boundary between the neural plate and the surface ectoderm (the neural plate border)
When does the neural plate form in embryogenesis in humans?
Week 3-5
How do we know that all the main different parts begin to be established early on in embryogenesis?
Can ‘tag’ specific molecules using antibodies, complimentary to proteins expressed:
Reveals organisation/regionalisation/development of specific regions
Not all the cells are the same - different transcriptional profile and therefore different proteins
What does convergent extension cause?
- Anterior endoderm and prechordal mesoderm to lie underneath one end of the neural plate
- Notochord to lie underneath the other end
How are the signals secreted from the anterior endoderm and axial mesoderm different?
TFs from the anterior endoderm and prechordal mesoderm induce ANTERIOR-TYPE transcription factors in the overlying neural plate cells
TFs from the notochord induce POSTERIOR-TYPE transcription factors in the overlying neural plate cells
What is sox2?
A highly conserved transcription factor which are expressed in cells that are on their way to adopt a neural fate
Where are sox2s expressed and when?
- In the neural plate
- Later confined to the forebrain (telencephalon, diencephalon)
- Just after the anterior endoderm/ prechordal mesoderm has involuted
What do TFs, such as sox2, determine?
Anterior fate of the neural plate
How does the neural plate get longer?
ACTIVATION-TRANSFORMATION MODEL:
- Signals from the notochord (underneath the neural plate) cause the back end of the neural plate to proliferate - BMPS?
- At the same time, DIFFERENT signals from the notochord transform these cells from an anterior to a posterior identity (represses Ant TFs) - Wnt, FGFs, RA etc
What is the ‘anterior CNS’?
Forebrain (telencephalon, diencephalon) and brain derivatives (eg. optic nerve)
What is the ‘posterior CNS’?
Hindbrain and spinal cord
How are BMP antagonists maintained in the prechordal mesoderm?
- By transcription factors siamois and goosegoid
In the anterior endoderm, what is induced by siamois and goosegoid and what do these molecules do?
Secreted molecules cerberus, frzb, dickkopf
Which inhibit the Wnt signalling pathway
What is needed in order to get anterior neural plate cells?
Inhibition of BMP AND Wnt signalling, by BMP and Wnt antagonists from the axial mesoderm
Where is Wnt signalling repressed?
In the neural plate, directly above the anterior endoderm
What do FGFs do and where are they high/low?
Maintain the proliferation of cells
Highest at the posterior end of the neural plate, low at the anterior - forms a gradient
What happens to Wnts at the notochord extends?
What does this form?
Wnts are upregulated
Forms a gradient, where Wnts are low anteriorly and high posteriorly
What causes the neural plate to posteriorise?
Upregulation of FGFs, Wnts and RA in a gradient manner as the notochord extends
Where does the extreme anterior fate arise? (forebrain)
What signal allows this?
Where there is NO Wnt signalling AT ALL
- Signals from the anterior endoderm (cerberus)
- Inhibits BMPs, Wnts and Nodal
What does retanoic acid do?
- Diffuse through the membrane and becomes bound by a cytoplasmic receptor
- When bound, goes through the pores in the nucleus adn binds to the promoters of genes
- Regulates gene transcription of HOX genes
What happens when RA is expressed in high concentrations compared to if low concentrations?
- Different subset of TFs turned on, dependant on the concentration of RA that the cells see
How is a gradient in the nervous system turned into step-like units (segmented)?
What model is this?
- Lewis Wolpert model
- X axis is distance from the source
- Y axis is concentration of the molecule
- Different cells respond differently to different threshold concentrations of the molecule by adopting different fates in a stepwise identity
(in relation to low, medium and high concentration)
What organisms is segmentation first seen in?
Segmented worms and drosophila larvae
What is segmentation controlled by in drosophila larvae and how?
Hox genes - expressed in different segmentation patterns in the forming embryo, control the segment identity of each domain
How do we know that hox genes specify AP segment identity in drosophila and provide positional information?
- Many different Hox genes
- Hox genes are evolutionarily conserved across species (with each hox gene having a homologue)
- Each hox gene is expressed in a specific region along the AP axis (from early stages of development through to adulthood)
- Up-regulated in response to RA
What are Hox gene up-regulated in response to?
Retanoic acid
Which Hox gene is turned on in responce to very high RA levels?
Hox 11
Which Hox gene is turned on in responce to very low RA levels?
Hox 5
What do Hox genes do?
Set the identity of the segment - tell which nerves to form (thoratic, lumbar, sacral,caudal etc)
What causes segmentation of the drosophila nerual axis?
- Retanoic Acid concentration gradient from low at the anterior end, to high at the posterior end
- Different levels of RA determines which Hox genes are upregulated (expressed)
- Changes the transcriptome, fate and function of that cell
- Different Hox genes confer different identities to the segment, in regards to neurons etc
What happens if knock out the genes which code for Hoxa1 and Hoxb1?
What does this show?
- Fail to get rhombomere 4
- Fail to get facial neurons
- Shows that Hoxa1 and Hoxb1 are required to specify rhombomere 4
What are rhombomeres?
‘Bulges’ of the developing brain
What induces midbrain cells?
An interaction at the boundary between the forebrain and hindbrain cells
Why are there multiple Hox genes which all code for the same protein in humans?
As a ‘back up’ incase one Hox gene fails
In the embryo, where does Sox2 eventually become confined to?
The forebrain - diencephalon, telencephalon
What does cerberus do?
Inhibits Wnt, BMP and nodal
Induces extreme anterior fate - forebrain
What does the procencephalon become?
- Dienchephalon
- Telenchephalon
What is the procencephalon?
Developing forebrain
What does the rhombencephalon become?
Metencephalon
Myelencephalon
What is the rhombencephalon
Developing hindbrain
