9357328 Abate This NSF Young Investigator (NYI) Award investigates the molecular mechanisms that control gene expression in the developing murine embryo using the hox gene family as a model system. The hox genes are expressed in overlapping spatial and temporal patterns throughout murine embryogenesis and play a fundamental role in controlling developmental processes. These encode putative transcriptional regulators; however, their function as such has not been well characterized. In particular, target genes that are regulated by Hox proteins during embryogenesis have not been identified. Moreover, it is not well understood how these related polypeptides, which share similar binding specificities in vitro, interact selectively with DNA regulatory elements in the control regions of target genes. The focus of my research is to identify such target genes and, in the course of this analysis, to investigate the molecular processes that promote target gene selection. The specific plan is to isolate genomic DNA fragments that contain binding sites for the Hox proteins and are potential regulatory sites in vivo. These studies will provide fundamental information concerning the function of these transcriptional regulatory proteins, as well as general insight into the mechanisms that control gene expression during embryogenesis. The goal of this research is to understand the processes that are required to direct the development of the mammalian nervous system. The assemblage of a system as complex as the nervous system requires many signals that are active in prcisely the right cell populations and at precisely the right times during development. A family of proteins, termed the Hox family, directs the appropriate expression of these signals (or genes) during development. These proteins are essential for normal development and any loss of function of these results in gross developmental abnormalities. Hox proteins function by interacting with DNA regul atory elements within the genes and thereby activating (or repressing) the expression of these genes. These studies will provide a basis for understanding how appropriate gene expression contributes to the development of the mammalian nervous system. ***
