Jean De Vellis, Ph.D.
Department of Psychiatry 635 Charles Young Drive, Room 375D NRB Los Angeles, CA 90095-7332 (Campus Mail Code 733222)
Regulation of Gene Expression in Brain Cells My laboratory is interested in the molecular mechanisms controlling neuronal and glial cells interaction during development. What are the environmental signals and the mechanisms that regulate the system events that fashion the progression of the multipotential neuroepithelial cells into the enormous cellular phenotypic diversity of the nervous sytems? We have developed rat brain culture system capable of recapitulating important developmental events of glial cells and neurons. These model systems have been used to identify growth factors and other agents that regulated proliferation, survival and differentiation in a cell specific manner. In this way, many environmental signals and numerous cell processes have been correlated with the appearance of different neural phenotypes. The expression of regulatory genes such as transcription factors particularly those who are lineage restricted, are regulated in a combinatorial manner by growth factors, hormones, neurotransmitters and cytokines. This research has helped define at the molecular level the plasticity of brain cells and their potential for regeneration. Regeneration in dysmyelinating rat mutants has been achieved by transplantation of glia progenitor cells. A main focus of the laboratory is on development of the oligodendrocytes, the myelin forming cells in the central nervous system and a key cell in brain iron homeostasis. The growth factors and other agents studied include neurotrophins, (NGF, BDNF, NT3) basis fibroblast growth factor, platelet-derived growth factor, transferrin, glucocorticoid hormones, retinoic acid and various cytokines known to be active in the immune system. Recent findings suggest that astrocytes microglia and neurons provide key signals for oligodendrocyte survival and differentiation.