Introducing the brain: making different neurons (Introduction)

by David Turell , Thursday, September 23, 2021, 19:35 (1155 days ago) @ David Turell

The process for making different neurons:

https://medicalxpress.com/news/2021-09-neuron-reveals-cellular-diversity-emerges.html

"Now, researchers at the Broad Institute of MIT and Harvard and the Flatiron Institute have shown how two key cell types in the brain's cortex arise from a single progenitor in mice. Led by Kathryn Allaway, Orly Wapinski, and Gord Fishell of the Stanley Center for Psychiatric Research at Broad, as well as Mariano Gabitto and Richard Bonneau of the Flatiron Institute, the researchers have discovered genetic and molecular factors that allow the two populations of interneurons to develop different identities.

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"Interneurons are neurons located exclusively in the central nervous system, and are more diverse in shape, connectivity, and function than any other type of cell in the front of the brain. The two most prominent types of interneurons are parvalbumin (PV)- and somatostatin (SST)-positive cells. In adults, these cells could not be more dissimilar.

"While both are inhibitory cells—they stop or slow down neuronal firing—PV and SST cells do this in different ways. PV cells act as a kind of veto, stopping a signal altogether, whereas SST cells fine-tune neuronal communication, allowing some signals to go through while halting others.

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"By comparing gene regulatory networks for different time points before and after birth, the team found that the two interneuron types diverged when they stopped migrating during early development and settled in the cortex. They found that certain proteins called transcription factors, which help regulate gene activity, were shared in both cell types but acted differently to direct development of the two cell types. This suggests that chromatin architecture plays a major role in maintaining the ultimate fate of the cells by controlling which transcription factors can access DNA to regulate gene expression. (my bold)

"Using their computational models, Fishell's team was then able to predict the impact of certain genes on cell type development. In particular, they found that the Mef2c gene, which is mutated in a severe form of autism, was involved in sculpting chromatin in both PV and SST cells but was particularly critical for PV cells. When the team disabled Mef2c in cells in the lab, they confirmed that their model accurately predicted 80 percent of the molecular targets that are regulated by Mef2c in both SST and PV cells."

Comment: My bold notes the importance of 3-D relationships. These relationships have to be deigned for proper gene expression for controlled activation by neighboring sites. This offers more insight into the embryology of the brain.