BONE MORPHOGENETIC PROTEIN REGULATION--BRAIN DEVELOPMENT

The long-term goal in applying for a clinical investigator development award is to enable the applicant to develop the analytic and technical skills necessary to become an independent investigator of clinically relevant basic science. The scientific aim Of this proposal is to further define mechanisms of intercellular communication in brain development. The investigation will focus on the role of the bone morphogenetic proteins (BMPs) in neural development. The BMPs are expressed in embryonic, postnatal, and adult mouse brains. Further, the BMPs have potent effects on the development of neurons and astrocytes in vitro. To examine the hypothesis that the BMP's play a role in the lineage commitment of neural progenitors and regulate the differentiation and function of more mature neural cells, the effects of the BMPs will be examined in vitro on cultured CNS progenitor cells, neurons and astrocytes. The developmental expression profiles of BMPs 2, 4 and 7, and the BMP receptors, activin receptor-like kinases (ALK) 3 and 6, will be determined. These investigations are significant both for defining basic developmental mechanisms relevant to CNS diseases, and for potentially leading to clinical applications for neurotrophic factors.