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

Sox结构域和同源结构域蛋白：果蝇神经系统DV模式的协调调节阐明调节中枢神经系统发育的分子途径对我们理解神经系统的形成和功能至关重要。 在人类中，神经元发育和功能的缺陷导致各种各样的先天性和遗传性神经系统疾病。 调节中枢神经系统发育的遗传和分子事件目前正在脊椎动物和无脊椎动物模型系统中探索。 这项工作的初步见解表明，在发育中的中枢神经系统和脊椎动物/哺乳动物同源基因表达的果蝇基因之间的结构，表达和功能显着的保护。 这些研究支持了这样一种观点，即许多生物过程的基本结构在苍蝇和人类之间是保守的。 这项资助的重点是阐明早期果蝇胚胎中枢神经系统模式的分子基础。 具体而言，表达和功能的一组进化保守的转录因子，统称为柱状基因/蛋白质，细分为三个纵向域的早期果蝇中枢神经系统从不同的神经元群体出现。 为了了解这些蛋白质如何将发育中的CNS划分为不同的结构域，必须鉴定柱状蛋白的调控靶点，并阐明柱状蛋白如何在分子水平上调节这些基因的区域特异性表达。然而，迄今为止，还没有发现这样的靶基因。 该提案的重点是鉴定柱状基因的直接调控靶点，并对这些基因的调控区域进行解剖，以便初步了解果蝇胚胎中早期CNS的分子机制。 值得注意的是，果蝇柱状基因和它们的哺乳动物对应物在果蝇和哺乳动物早期CNS的初始模式化过程中分别发挥几乎相同的作用。 因此，这是可能的，通过这些转录因子调节模式在果蝇中枢神经系统的分子机制的澄清将有深远的影响，我们了解哺乳动物中枢神经系统的发展。

Sox-domain and Homeodomain proteins: CoordinateRegulation 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.