The mechanism of hmgcr-dependent germ cell migration

hmgcr依赖性生殖细胞迁移机制

• 批准号: 6339521
• 负责人: VALARIE E MILLER-BERTOGLIO
• 金额: $ 1.12万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6339521
• 关键词: Drosophilidae; HMG coA reductases; biological signal transduction; cell migration; enzyme activity; gene complementation; gene mutation; genetic mapping; genetic recombination; genetic screening; germ cells; gonads; histogenesis; microinjections; phenotype; site directed mutagenesis

In a number of species the primordial germ cells (PGCs) originate separate from the somatic gonad. During early embryonic development, the PGCs migrate through somatic tissues to their target, the gonadal primordia. The directed migration of PGCs is an active process, thought to be mediated by both attractive and repulsive signals. 3-hydroxy-3- methylglutaryl coenzymeA reductase (HMGCR), a general metabolic enzyme, is both necessary and sufficient to attract migrating germ cells. How HMGCR mediates the guidance of germ cells along a highly characteristic path is not known. The goal of the proposed work is to characterize the role of HMGCR in directing Drosophila PGC migration using both pharmacological and genetic approaches. Pharmacological reagents, including inhibitors of well characterized pathway branches downstream of HMGCR, provide a directed means of identifying which branch of the highly branched pathway is mediating PGC guidance. To identify genetic loci that act downstream of hmgcr, a genetic screen for mutations that dominantly enhance the mild migratory defects of a weak mutation in hmgcr will also be carried out. These experiments will aid in identifying the molecular nature of a germ cell guidance signal produced by the HMGCR pathway and how germ cells receive this signal.

在许多物种中，原始生殖细胞（PGCs）与体细胞性腺分开起源。在早期胚胎发育过程中，PGCs通过体细胞组织迁移到它们的目标，性腺原基。PGC的定向迁移是一个活跃的过程，被认为是由吸引信号和排斥信号介导的。3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）是一种常见的代谢酶，它是吸引迁移的生殖细胞所必需的。HMGCR如何介导生殖细胞沿着沿着高度特征性的路径的引导尚不清楚。拟议的工作的目标是表征的作用HMGCR在指导果蝇PGC迁移使用药理学和遗传学的方法。药理学试剂，包括HMGCR下游充分表征的途径分支的抑制剂，提供了鉴定高度分支化途径的哪个分支介导PGC引导的直接手段。为了鉴定作用于hmgcr下游的遗传基因座，还将对显性增强hmgcr弱突变的轻度迁移缺陷的突变进行遗传筛选。这些实验将有助于确定由HMGCR途径产生的生殖细胞指导信号的分子性质以及生殖细胞如何接收该信号。