2nd year recap Flashcards
What is neurogenesis?
The growth and development of the nervous tissue
When does neural patterning and neurogenesis occur?
When is this process in humans?
After the formation of the neural tube from the neural plate
Between 4-12 weeks
How does the neural plate roll up to become the neural tube?
At what somite stage?
NOT uniform:
- First to roll up becomes the HINDBRAIN
- Lots of morphogenesis
0-3 somite stage
What is spinal bifida?
When the spinal cord doesn’t close
Where is the neural tube wider? Why?
At the BRAIN - due to more cell proliferation
What breaks the symmetry of the neural tube?
Differential proliferation (more are the brain)
How do neurons form?
What is this governed by?
What does this determine?
Same as cell differentiation in any part of the body:
- Cells become DIFFERENT from each other and ACQUIRE SPECIALISED properties
- Governed by CHANGES in GENE EXPRESSION, which dictate the REPERTOIRE of protein synthesised
- REPERTOIRE of proteins translated dictate a cells BEHAVIOUR (eg. proliferation, migration etc)
How do CHANGES in GENE EXPRESSION dictate the REPERTOIRE of protein synthesised?
Determine which proteins are transcribed and translated into protein and determine which proteins are actively repressed
What happens to the potency of a cell over time? Why?
Potency is REDUCED - cells become more specialised/differentiated as repertoire of protein changes
What 2 things are gene expression (repertoire of proteins/genes) in a cell governed by?
1) EXTRINSIC factors (morphogens and signals)
2) INTRINSIC factors (transcription factors)
When does differentiation occur?
Over TIME as CELLS DIVIDE
What cells are neurons born from?
Progenitor cells
What are progenitor cells?
Cells that are slightly more specialised than stem cells but aren’t fully committed (have lost some potency)
Tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its “target” cell
Where is the action of TF important?
In progenitor cells
As progression of a cell occurs, what does the cell become dependant on?
TF (switch from morphogens)
What causes the differentiation of neurons?
Secreted morphogens and intrinsic transcription factors
What does ISH of shh mRNA in the neural tube show?
Shh is NOT INITIALLY expressed in the neural tube itself
1) INITIALLY expressed in a rod of mesoderm that lies beneath the ventral midline of the neural tube
2) Then shh is expressed in a triangular shaped region at the ventral midline (floor plate)
What does shh code for?
A SECRETED protein
What experimental procedure allows to see protein?
Antibody labelling experiment (make antibody against the protein)
What does an antibody labelling experiment of shh show?
- Shh expressed in the notochord and floor plate and in cells next to the floor plate (extending dorsally)
Shows shh:
- Is secreted from cells making it and extends dorsally
What type of molecule does shh act as?
What does this do?
Acts as a MORPHOGEN
To induce different progenitor cells along the dorso-ventral axis of the future spinal cord
What is a morphogen?
A SECRETED protein which establishes a CONCENTRATION GRADIENT
How do cells respond to a morphogen gradient?
Cells respond DIFFERENT THRESHOLDS of morphogen and respond DIFFERENTLY by eliciting DIFFERENT programmes of GENE EXPRESSION - make cells different
What is the difference between a stem cell and a progenitor cell?
PC only has a LIMITED NUMBER of cell divisions that it can make before it eventually differentiates
How does a progenitor cell become a certain type of neuron?
Due to the TF profile elicited at an earlier point in time
What does high concentrations of shh do?
REPRESSES cell cycle genes - limiting cell divisions
What are the readouts of shh along the DV axis of the neural tube?
5 BANDS of progenitor domains expressing specific TFs
When do cells along the DV axis of the neural tube begin to be different to each other?
When the express different TF as a result of shh gradient
Describe ‘cellular memory’
As progenitor divides - daughters know who they are
What do TF ‘code’?
Later differentiation:
- Different character of the cells depending on what cell they came from
How do progenitors divide?
What do the daughters become?
With asymmetry:
- Daughters stay close to the LUMEN as a PROGENITOR
- Other daughter migrates LATERALLY outwards to build up the radial dimension (width)
How are neurons arranged along the DV axis of the neural tube?
What determines what neurons?
Different classes of neurons arranged with bilateral symmetry:
- Motor ventrally
- Middle - different classes of relay neurons
- Anterior - commissural relay neurons
Determined by the progenitor they came from and which TF were expressed in the progenitor cell, determined by the threshold of shh the cells see
Why is the top of the neural tube thinner than the ventral?
Due to shh effects on the cell cycle????
What molecule sets up the progenitor domains at the dorsal of the neural tube?
BMP/Wnts
Ultimately, how many progenitor domains line the neural tube?
10 (5 - shh, 5 BMP/Wnts)
Why do axons project to different places as progenitors differentiate?
What are these determined by?
Different axons have different receptors which are determined by the TF the progenitors express
Why do commissural axons migrate to the floor plate but motor axons don’t?
Motor axons don’t have netrin receptors but commissural axons do
How are neuronal circuits formed?
Function as neurotransmitters cross synapses
What is the NT expressed by a cell a feature of?
The TF expressed by the grandmother cell
