Role of Dorsal Forerunner Cells in Left/Right Patterning

描述(由申请人提供)： 胚胎发育过程中的左/右(L/R)模式缺陷常导致复杂的先天性心脏缺陷。脊椎动物胚胎最初确定L/R轴的机制(S)尚不清楚。来自老鼠和斑马鱼模型的证据表明，胚胎单丝细胞产生了一种向左流动的液体，介导了L/R的发育。以斑马鱼为模型系统，将采用正向和反向遗传方法来识别调节产生向左流动的单纤毛细胞(背侧前体细胞)的专门域的基因。被识别的影响向左血流的基因可能被认为是偏侧缺陷的候选基因。最近，有人提出，向左流动激活了胚胎左侧的机械感觉单丝。电子显微镜和共聚焦显微镜将被用来表征背侧前体细胞单纤毛的结构和分子性质，并测试机械感觉纤毛是否参与L/R的构型。

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.