Sox-Domain and Homeodomain Proteins: Coordinate Regulation of DV Patterning of the Drosophila Nervous System

Washington University School Of Medicine, Saint Louis MO

Investigators

Abstract

Sox-domain and Homeodomain proteins: Coordinate Regulation of DV patterning of the Drosophila Nervous System. The elucidation of the molecular pathways that regulate the development of the central nervous system is critical to our understanding of nervous system formation and function. In humans, defects in neuronal development and function lead to a wide variety of congenital as well as inherited neurological diseases. The genetic and molecular events that regulate CNS development are just now being explored in vertebrate and invertebrate model systems. Initial insights from this work demonstrate a remarkable conservation of structure, expression and function between Drosophila genes expressed in the developing CNS and their vertebrate/mammalian homologs. These studies support the idea that the fundamental architecture of many biological processes are conserved between flies and humans. The focus of this grant is to elucidate the molecular basis of CNS patterning in the early Drosophila embryo. Specifically, the expression and function of a set of evolutionarily conserved transcription factors, collectively referred to as the columnar genes/proteins, subdivides the early Drosophila CNS into three longitudinal domains from which distinct neuronal populations arise. In order to understand how these proteins partition the developing CNS into distinct domains it is essential to identify regulatory targets of the columnar proteins and to elucidate how the columnar proteins act at the molecular level to regulate the regions specific expression of these genes. However to date, no such target genes have been identified. This proposal focuses on the identification of direct regulatory targets of the columnar genes and on the dissection of the regulatory regions of these genes in order to provide an initial glimpse into the molecular mechanisms that pattern the early CNS in the Drosophila embryo. Of note, the Drosophila columnar genes and their mammalian counterparts perform nearly identical roles during the initial patterning of the Drosophila and mammalian early CNS, respectively. Thus, it is likely that the clarification of the molecular mechanisms through which these transcription factors regulate pattern in the Drosophila CNS will have far reaching implications for our understanding of CNS development in mammals.