Role of Dorsal Forerunner Cells in Left/Right Patterning

描述（由申请人提供）： 在胚胎发育过程中左/右（L/R）图案事件的缺陷通常会导致复杂的先天性心脏缺陷。L/R轴最初在脊椎动物胚胎中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，胚胎单眼产生介导L/R发育的液体的快速流动。使用斑马鱼作为模型系统，正向和反向遗传方法将被用来识别调节产生微流的单纤毛细胞（背侧前体细胞）的专门结构域的基因。影响脑血流的基因可能被认为是偏侧性缺陷的候选基因。最近，有人提出，反流激活胚胎左侧的机械感觉性单眼。电子和共聚焦显微镜将被用来表征背前体细胞的结构和分子特性的monocilia和测试是否mechanosensory纤毛参与L/R图案。

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.