Cytokinesis and RNA Segregation in Zebrafish Development

斑马鱼发育中的细胞分裂和 RNA 分离

• 批准号: 7368460
• 负责人: FRANCISCO J PELEGRI
• 金额: $ 27.85万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7368460
• 关键词: Actins; Address; Affect; Animals; Binding; Biology; Calcium Oscillations; Cell Separation; Cell division; Cell physiology; Cells; Classification; Code; Coupled; Cytokinesis; Cytoplasm; Data; Development; Developmental Process; Drosophila polo protein; Embryo; Embryonic Development; Exocytosis; Genes; Germ; Germ Cells; Growth and Development function; Health; Individual; Island; Kinesin; Knowledge; Lateral; Lead; Life; Link; Localized; Medial; Mediating; Mediator of activation protein; Membrane; Messenger RNA; Microtubules; Modeling; Molecular; Mutation; Nature; Organism; Pathway interactions; Pattern; Phosphotransferases; Process; Proteins; RNA; Regulation; Reproductive Biology; Research; Role; Sampling; Signal Transduction; Structure; Testing; Tissues; Zebrafish; aurora B kinase; base; cancer stem cell; cell type; daughter cell; insight; physical process; protein expression; segregation

DESCRIPTION (provided by applicant): Cytokinesis, the physical process that divides daughter cells, is of critical importance to development and growth regulation. In many instances, cytokinesis is coupled with the asymmetric segregation of cellular determinants, which in turn results in the functional diversification of cell types. A basic question in biology is to understand the molecular mechanisms underlying the segregation of cell fate determinants, in particular the germ plasm, a specialized cytoplasm that confers the germ cell fate. Systematic screens for maternal-effect mutations in the zebrafish, Danio rerio, have identified genes that affect the processes of cytokinesis and germ plasm segregation, which in this organism are intimately linked. To our knowledge, these are the first identified mutations in vertebrate genes required for cytokinesis. This proposal focuses on the analysis of the function of one of these genes, Cellular Island, which we show codes for Aurora B kinase, a chromosomal passenger protein involved in furrow initiation. Functional analysis of this gene suggests that it has an essential role in furrow formation in lateral, but not medial, regions of the embryonic blastodisc. We will test the hypothesis that furrow-inducing signals from different microtubule-based structures, possibly through the action of distinct downstream mediators such as Aurora B kinase, are required for cytokinesis in separate regions of the blastodisc. The proposed research will also determine the precise roles of these signals in the process of germ plasm recruitment to the forming furrow. The understanding of these mechanisms will provide insights on both a fundamental cellular process (cytokinesis) and a fundamental developmental process (germ plasm segregation), and the functional relationship between them in the early vertebrate embryo. The proposed research addresses fundamental mechanisms of cell division and the determination of cell fate, in particular, the specification of the germ cells. Knowledge acquired through these studies will lead to progress in therapies that alleviate health problems related to reproductive biology, cancer, and stem cell and tissue development.

描述（由申请人提供）：胞质分裂是分裂子细胞的物理过程，对发育和生长调节至关重要。在许多情况下，胞质分裂与细胞决定簇的不对称分离相结合，这反过来又导致细胞类型的功能多样化。生物学中的一个基本问题是了解细胞命运决定因素分离的分子机制，特别是种质，一种赋予生殖细胞命运的特殊细胞质。系统筛选斑马鱼的母体效应突变，Danio rerio，已经确定了影响胞质分裂和种质分离过程的基因，这在这种生物体中是密切相关的。据我们所知，这些是第一个确定的突变脊椎动物基因所需的胞质分裂。这项建议的重点是分析这些基因之一，细胞岛，我们显示极光B激酶，一个染色体乘客蛋白参与犁沟起始的代码的功能。该基因的功能分析表明，它在胚胎胚盘的外侧而非内侧区域的沟形成中具有重要作用。我们将测试的假设，沟诱导信号从不同的微管为基础的结构，可能通过不同的下游介质，如极光B激酶的作用，所需的胞质分裂在不同地区的胚盘。拟议的研究还将确定这些信号在胚质补充到形成沟的过程中的确切作用。这些机制的理解将提供见解的基本细胞过程（胞质分裂）和基本的发育过程（种质分离），以及它们之间的功能关系在早期脊椎动物胚胎。 拟议的研究涉及细胞分裂的基本机制和细胞命运的决定，特别是生殖细胞的特化。通过这些研究获得的知识将导致在缓解与生殖生物学、癌症、干细胞和组织发育有关的健康问题的疗法方面取得进展。