Role of Dorsal Forerunner Cells in Left/Right Patterning

背侧先行细胞在左/右图案形成中的作用

• 批准号: 6738235
• 负责人: JEFFREY D AMACK
• 金额: $ 4.3万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-22 至 2007-01-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6738235
• 关键词: biological models; biological signal transduction; calcium; cardiogenesis; cilium; confocal scanning microscopy; congenital cardiovascular disorder; developmental genetics; egg /ovum; electron microscopy; embryo /fetus; fluid flow; fusion gene; postdoctoral investigator; site directed mutagenesis; zebrafish

DESCRIPTION (provided by applicant): Defects in left/right (L/R) patterning events during embryonic development often lead to complex congenital heart defects. The mechanism(s) by which the L/R axis is initially specified in the vertebrate embryo remain unclear. Evidence from mouse and zebrafish models suggest embryonic monocilia create a leftward flow of fluid that mediates L/R development. Using zebrafish as a model system, forward and reverse genetic approaches will be taken to identify genes that regulate the specialized domain of monociliated cells (dorsal forerunner cells) that generate leftward flow. Genes identified that affect leftward flow may be considered candidates for laterality defects. Recently, it has been proposed that leftward flow activates mechanosensory monocilia on the left side of the embryo. Electron and confocal microscopy will be used to characterize the structural and molecular properties of dorsal forerunner cell monocilia and test whether mechanosensory cilia are involved in L/R patterning.

描述（由申请人提供）： 胚胎发育过程中左/右（L/R）模式事件的缺陷通常会导致复杂的先天性心脏缺陷。脊椎动物胚胎中 L/R 轴最初被指定的机制仍不清楚。来自小鼠和斑马鱼模型的证据表明，胚胎单纤毛会产生向左流动的液体，从而介导左/右发育。使用斑马鱼作为模型系统，将采用正向和反向遗传方法来识别调节单纤毛细胞（背侧前驱细胞）产生左向流动的特殊域的基因。确定的影响左流的基因可以被认为是偏侧性缺陷的候选基因。最近，有人提出向左流动激活胚胎左侧的机械感觉单纤毛。电子和共聚焦显微镜将用于表征背侧前驱细胞单纤毛的结构和分子特性，并测试机械感觉纤毛是否参与 L/R 模式。