The goal of this work is to determine if a novel protein, is implicated in cellular death, survival or both in the mouse nervous system. For many years, the Schwartz laboratory has taken advantage of intersegmental muscles of moth as a model system to clone death-associated transcripts. Many of the genes isolated during this research are structurally and functionally conserved among diverse taxa and may serve as regulators of both cell death and survival. One of these genes, 44a, shares 31 percent identity and 40 percent similarity between moth and man. Functional studies strongly support the hypothesis that 44a functions as a new human oncogene. Radiation hybrid mapping of 44a in human suggests that it could be a candidate gene in Bardet-Biedel Syndrome, an autosomal recessive disorder that results in mental retardation polydactyly, syndactyly, hypogenitalism and diabetes. Preliminary studies utilizing in situ hybridization indicate that 44a is predominantly expressed in the central nervous system and that it is differentially expressed in the embryonic brain during critical periods of organizational plasticity. This work can be divided into two Specific Aims. The first will utilize in vivo techniques to determine if 44a is regulated before, during or after developmental neuronal plasticity and determine in which cellular phenotypes it is expressed.
The second Aim will use in vitro techniques to causally test the role of 44a in cellular proliferation and differentiation. In order to achieve these Aims, the applicant will receive general training in developmental aspects of biology as well as extensive training in cell culture, transduction and transfection studies, in situ hybridization, cloning, antibody production and FACscan. In addition, the applicant will expand upon her neuro-anatomical and biological training as part of Aim I. Together these skills will enable the applicant to pursue both in vitro and in vivo questions.
