MOLECULAR GENETICS OF NERVOUS SYSTEM DEVELOPMENT

神经系统发育的分子遗传学

• 批准号: 2270278
• 负责人: JOHN ROBERT NAMBU
• 金额: $ 9.52万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2270278
• 关键词: Drosophilidae; complementary DNA; developmental genetics; developmental neurobiology; gene induction /repression; gene mutation; genetic markers; glia; invertebrate embryology; neurogenesis; neurons; nucleic acid sequence; oligonucleotides; restriction mapping; transcription factor

The body plan of many animals exhibit bilateral symmetry; this is often reflected in the organization of the nervous system. In both insects and vertebrates the cells which lie along the midline of the nervous system are specified early in development and go on to exhibit distinctive morphologies, patterns of gene expression, and functions. In Drosophila, the embryonic CNS midline is comprised of approximately 25 neurons and glia per segment which play crucial roles int he proper elaboration of the CNS axon scaffold as well as in establishing the identities of neighboring epidermal cells. These cells comprise a discrete, highly accessible cellular subsystem with which to study nerve cell development. Our major interests lie in better understanding the development and function of specific nervous system cell types. Towards this end we will investigate the developmental pathways by which cells of the Drosophila CNS midline differentiate and come to acquire unique functional properties. This will involve molecular genetic analyses of the roles of several genes, including single-minded, other spitz class genes, and a novel midline glial expressed gene, AA41, both in the differentiation of midline neurons and glia and a midline derived signaling pathway required for proper development of the ventral epidermis. These studies will have general implications for understanding the development and function of related midline nervous system structures in other species, such as the vertebrate floor plate and roof plate. In addition, they may shed light onto a series of human genetic and epigenetic birth defects, the holoprosencephalies, which result in midline defects in craniofacial development.

许多动物的身体结构呈现出左右对称性。这常常是 反映在神经系统的组织上。 在昆虫和 脊椎动物位于神经系统中线的细胞 在开发早期就被指定并继续表现出独特的 形态、基因表达模式和功能。 在果蝇中， 胚胎中枢神经系统中线由大约 25 个神经元组成 每个片段的神经胶质细胞在正确阐述中起着至关重要的作用 CNS 轴突支架以及确定 邻近的表皮细胞。 这些细胞包含一个离散的、高度 可用于研究神经细胞发育的细胞子系统。 我们的主要兴趣在于更好地了解发展和 特定神经系统细胞类型的功能。 为此我们将 研究果蝇细胞的发育途径 CNS中线分化并获得独特的功能 特性。 这将涉及角色的分子遗传学分析 几个基因，包括专一的、其他斯皮茨类基因，以及 一种新的中线胶质细胞表达基因 AA41，均在分化过程中 中线神经元和神经胶质细胞以及中线衍生的信号通路 腹表皮正常发育所必需的。 这些研究 对于理解发展和 其他物种相关中线神经系统结构的功能， 例如脊椎动物的底板和顶板。 此外，他们可能 揭示了一系列人类遗传和表观遗传出生缺陷， 前脑无裂，导致颅面中线缺损 发展。