Differential Actin Regulation in Zebrafish Development

斑马鱼发育中的差异肌动蛋白调控

• 批准号: 7011234
• 负责人: DAVID F DAGGETT
• 金额: $ 5.8万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7011234
• 关键词: actins; biological signal transduction; chimeric proteins; confocal scanning microscopy; embryo /fetus; embryogenesis; genetically modified animals; growth /development; guanine nucleotide exchange factors; histogenesis; immunocytochemistry; mesoderm; postdoctoral investigator; protein protein interaction; protein structure function; zebrafish

DESCRIPTION (provided by applicant): The proposed research seeks to understand how the spatial and temporal control of actin dynamics is regulated differentially across the developing vertebrate embryo. This will be investigated within the specific context of mesodermal cell behaviors during gastrulation and segmentation in the zebrafish embryo. The potential role of actin regulatory molecules (ARMs) that are expressed in specific areas of developing mesoderm will be investigated by loss of function analysis, using confocal imaging and a transgenic line of reporter fish expressing actin-GFP fusion protein that reveals cellular actin distribution. The signaling pathways controlling these ARMs will be characterized using mutagenesis screening and protein-protein interaction assays. The misregulation of actin and cell movements has been implicated in multiple human conditions such as Wiskott- Aldrich syndrome and Spina Bifida, in which compromised cell polarity causes a failure of neural tube closure in early development. An understanding of actin regulation during vertebrate development in the zebrafish may thus provide insights into the causes and treatment of certain human diseases.

描述（由申请人提供）： 拟议的研究旨在了解肌动蛋白动力学的空间和时间控制如何在发育中的脊椎动物胚胎中受到差异性调节。这将在斑马鱼胚胎原肠胚形成和分割过程中中胚层细胞行为的特定背景下进行研究。在发育中胚层特定区域表达的肌动蛋白调节分子（ARM）的潜在作用将通过功能丧失分析进行研究，使用共焦成像和表达肌动蛋白-GFP融合蛋白的转基因报告鱼系，揭示细胞肌动蛋白分布。将使用诱变筛选和蛋白质-蛋白质相互作用测定来表征控制这些 ARM 的信号通路。肌动蛋白和细胞运动的失调与多种人类疾病有关，例如威斯科特-奥尔德里奇综合征和脊柱裂，其中细胞极性受损导致早期发育中神经管闭合失败。因此，了解斑马鱼脊椎动物发育过程中肌动蛋白的调节可能有助于了解某些人类疾病的原因和治疗。