Nuclear Receptors in Neural Stem Cells and Adult Neurogenesis
The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behavior. We have shown that TLX maintains adult neural stem cells in an undifferentiated, self-renewable state. While TLX-expressing cells isolated from adult brains can proliferate, self-renew, and differentiate into all neural cell types in vitro, TLX-null cells isolated from adult mutant brains fail to proliferate. In vivo, TLX mutant mice show a loss of cell proliferation and reduced neural progenitors in the neurogenic areas of adult brains
Our primary research focuses on neural stem cells in the adult brain — specifically, we are interested in characterizing the molecular cascades that program these cells to remain in the stem cell state, or that cause them to differentiate and become neurons. An understanding of the molecular basis of stem cell regulation will provide insights into how stem cells are maintained and how they are stimulated to differentiate. Armed with this knowledge, researchers will be able to develop new, targeted therapies for a whole host of neurological disorders, including brain injuries, brain tumors, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases.