Researchers find single gene that controls brain cell development - Could augment it to combat diseases, etc.

Scientists at the Institute of Molecular Biology (IMB) in Mainz, Germany have unraveled a complex regulatory mechanism that explains how a single gene, NeuroD1, can drive the formation of brain cells. The research, published in The EMBO Journal, is an important step towards a better understanding of how the brain develops and may lead to breakthroughs in regenerative medicine.

Neurodegenerative disorders, such as Parkinson’s disease, are often characterized by an irreversible loss of brain cells.

ABSTRACT

Cell fate specification relies on the action of critical transcription factors that become available at distinct stages of embryonic development. One such factor is NeuroD1, which is essential for eliciting the neuronal development program and possesses the ability to reprogram other cell types into neurons. Given this capacity, it is important to understand its targets and the mechanism underlying neuronal specification. Here, we show that NeuroD1 directly binds regulatory elements of neuronal genes that are developmentally silenced by epigenetic mechanisms. This targeting is sufficient to initiate events that confer transcriptional competence, including reprogramming of transcription factor landscape, conversion of heterochromatin to euchromatin, and increased chromatin accessibility, indicating potential pioneer factor ability of NeuroD1. The transcriptional induction of neuronal fate genes is maintained via epigenetic memory despite a transient NeuroD1 induction during neurogenesis. NeuroD1 also induces genes involved in the epithelial‐to‐mesenchymal transition, thereby promoting neuronal migration. Our study not only reveals the NeuroD1‐dependent gene regulatory program driving neurogenesis but also increases our understanding of how cell fate specification during development involves a concerted action of transcription factors and epigenetic mechanisms.