Scientists uncover mechanism that explains how single gene drives brain development

The development of the brain is the result of a large number of genes orchestrating the differentiation of stem cells into various types of brain cell. Now, a new study reveals that the gene NeuroD1 is not only expressed in brain stem cells but also acts as the master regulator of this complex process.
nerve cells
The researchers say NeuroD1 creates an epigenetic memory in the cell of how it should differentiate as brain development unfolds.

Reporting in the The EMBO Journal, researchers from the Institute of Molecular Biology (IMB) in Mainz, Germany, describe how they unraveled the intricate mechanism through which NeuroD1 drives the formation of brain cells.

They believe their findings will not only improve understanding of how the brain develops and forms new cells, but they could also help develop regenerative treatments for Parkinson’s disease and other neurodegenerative disorders.

In neurodegenerative diseases like Parkinson’s and Alzheimer’s, brain function declines because of loss of cells that are not able to replace themselves, so the damage is permanent.

The aim of regenerative medicine is to replenish lost cells – for example, by replicating how the body creates new cells during development.

But the brain is a complex organ, and we do not know very much about its development at the molecular level.

The researchers at IMB have been studying the role that NeuroD1 plays in brain development. They had already established that the gene is active at the very start of the brain development process.

Master gene creates ‘epigenetic memory’ in cells

In the new study, the researchers found that NeuroD1 acts like a master switch that launches the brain development process.

They found that NeuroD1 controls other genes by altering their “epigenetic” state – without altering their underlying DNA, it leaves markers on the genes that show whether they are switched on or off and that influence how they are read.

However, another important feature they discovered is that NeuroD1 continues to influence this process even when it switches off. The epigenetic markers it leaves on the other genes are permanent.

It is as though NeuroD1 creates an “epigenetic memory” in the cell of how it should differentiate as brain development unfolds. Joint first authors Abhijeet Pataskar and Johannes Jung explain:

“Our research has shown how a single factor, NeuroD1, has the capacity to change the epigenetic landscape of the cell, resulting in a gene expression program that directs the generation of neurons.”

Dr. Tiwari says the study is exciting because it does much to clarify what links DNA sequence, epigenetic changes and cell fate. Also, he concludes:

“It not only sheds new light on the formation of the brain during embryonic development but also opens up novel avenues for regenerative therapy.”

Meanwhile, Medical News Today recently learned how targeting the formation of unwanted blood vessels in the brain could be a way to help people with Parkinson’s disease who continue to have problems with balance and walking despite dopamine-restoring medication.

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