The long term goal of my research is to characterize the role of homeobox-containing genes in the development of the mammalian central nervous system, focusing on the spinal cord. The objective of this proposal is to study the structural organization and the expression of two unique rat homeobox-containing genes. These two genes are closely linked and have not been yet identified in other organisms and are expressed at high levels in the spinal cord and during embryogenesis. In general, the homeobox-containing genes are thought to be important in the control of positioning information during morphogenesis. Several features make the rat spinal cord attractive for the primary focus of this study. The rat spinal cord has been intensely studied; its anatomical structure, neuronal connections and physiological functions are well characterized. The spinal cord is composed of a wide diversity of cell types and has a complex internal organization. Yet, good correlations exist between the embryonic and adult structures of the spinal core, which is the least modified portion for the embryonic neural tube, making to relatively easy to follow the developmental pathway. This should provide a suitable research system for examining the role of homeobox-containing genes in neuronal development. We plan on studying the expressing of these genes using immunohistochemical and in situ hybridization approaches, which permit the localization of protein species and RMA transcripts, respectively, at the level of a single cell or single neuron. We will examine the spatial and temporal pattern of gene expression in the spinal cord during the course of embryogenesis. Completion of the specific aims of this research proposal will provide a first step in understanding the role of homeobox-containing genes in the central nervous system. Moreover, this set of genes will provide molecular markers for other studies in the central nervous system. Understanding the normal development of the spinal cord will provide insight into the problem os regenerating and embryonic cell transplantation in spinal cord reconstruction after traumatic injury.
