reproduced verbatim): The overall goal of these studies is to define the role of gap junctions in neural progenitor cell survival, proliferation, and commitment to neuronal and glial lineages, and in the progressive development of neurons and glia. The basic hypotheses underlying these studies are that gap junctional communication coordinates proliferation and survival of subpopulations of progenitor cells and orchestrates early lineage commitment, and that functional uncoupling of progenitor species is subsequently necessary for exit from cell cycle and commitment to specific lineages. Thereafter re-expression of other connexins with different biophysical properties influences cell function. The development of progenitor cells can be manipulated in vitro by changing the cellular microenvironment to promote neurogenesis or gliogenesis. The proposed studies will examine the functional role of gap junctions in regulating development of these populations in vitro, and will define connexin expression in the developing brain in vivo. They will examine the relationship between the regulation of gap junctional communication and exit of progenitor cells from cell cycle and the role of connexins in the subsequent maturation of neuronal progeny. They will define mechanisms that determine which connexin is expressed by developing neurons and whether the expression of gap junction channels with different biophysical properties alters the phenotype of developing neurons. Particular focus will be placed on the study of connexin 36, a major neuronal gap junction protein in the brain. These studies should provide insight into mechanisms regulating neural development, lineage commitment, and phenotypic expression, and into the role of gap junctions in regulating these processes.
