Transcriptional regulation of neurogenesis and neuronal fate specification Flashcards
By what characteristics, can neuron types be classified?
Morphology, localization, neurotransmitter identity, connectivity and activity patterns.
What are selector genes?
They regulate the terminal differentiation genes, that will mediate cellular function
What are terminal differentiation genes?
The genes that mediate cellular function
What are the most important transcription factor families in neurogenesis and differentiation?
SOX, HES/bHLH, HD/POU and HD/LIM
What is NRSE/RE1?
A motif in neuronal gene promoters, that can be bound by REST/NRSF which regulates their expression
What does the TF REST/NRSF bind?
The RE2/NRSE motif, found in neuronal gene promoters
What is most often the function of Sox TFs?
They enhance neuronal gene expression
What are the basic helix-loop-helix TFs important for neurogenesis?
Hes1-3 that maintain neuronal progenitors
What are the most important proneural genes?
Ascl1-4, Neurogenin1-2, Math1, Olig, NeuroD
What is the function of Hes TFs?
They maintain neuronal progenitors by repressing proneural gene expression
The balance of what two signals determine if a neuronal progenitor will exit the cell cycle and differentiate?
Proneural TFs (cause differentiation) and HES (maintain progenitor status)
What does the expression pattern of proneural and hes genes look like in neuronal progenitor cells?
There are oscillating levels of both types of genes.
What does the expression pattern of proneural and hes genes look like in differentiating neuronal cells?
proneural genes are upregulated, and hes genes are downregulated
What are the targets for proneural TFs, and what do they up and down regulate?
They upregulate cell cycle inhibitors, delta and other TFs, and they downregulate glial fate determinants.
What happens in the neighbouring cell of a differentiating neuron?
The delta expression on the differentiating cell will activate notch on its neighbour which will inhibit proneural genes (lateral inhibition)