Grant: Project Grant

The birth of new neurons, a process called neurogenesis, occurs throughout our entire life. Every day, new neurons are derived from neural stem cells which have the capacity to renew themselves endlessly. Indeed, even people in their eighties still grow new neurons! However, aging, stress or poor diet all can reduce the natural rate of neurogenesis. The challenge is to make the most of our brain, prevent our neurons from dying in old age and keep growing new ones in order to stave off neurodegenerative diseases. Therefore, we need to understand the mechanisms promoting the generation of neurons. Each cell contains about 20,000 genes on its DNA. Those genes spell out instructions for making proteins. Each gene may instruct different yet similar proteins through a process called alternative splicing. The genome is like an enormous cookbook of 20,000 recipes. It's as if a "recipe-reader" omits or replaces ingredients; the resulting dish from one recipe may be similar but taste differently! Now, the DNA molecule that carries all genes (the enormous cookbook) is about 2 meters long and needs to be condensed to fit into the nucleus. The DNA packaging renders access to the genes harder to make proteins. The writing in the book is difficult to read! Transcription factors (the "recipe-readers") help to recognize some specific genes, modify the condensation on them and allow the production of a variety of proteins essential for the birth of neurons. If "recipe-readers" are faulty, neurogenesis suffers. This project will focus on a transcription factor called GATA3. GATA3 is expressed in multiple areas of the brain and is important for the birth of different types of neurons. We wish to determine how GATA3 regulates DNA condensation of its target genes and how it controls the production of proteins. The findings will provide novel insights into mechanisms regulating the birth of neurons, and will help to develop new therapeutic strategies against neurodegenerative diseases.