Rab23 function in nodal signaling during left-right patterning in the mouse

描述（由申请人提供）：脊椎动物的身体平面图在发育过程中沿其左右轴绘制。这确保了器官在体内的位置不对称，并且单个器官，如心脏和肺，采用不对称结构。在我们的胚胎发育过程中，这一过程的失败会导致危及生命的疾病，如先天性心脏缺陷。左右模式在很大程度上是由胚胎左侧用于细胞间通讯的节点信号通路的不对称活动所控制的。在这里，我们研究Rab23蛋白在胚胎节点信号传导中的作用。缺乏Rab23的小鼠胚胎由于无法激活左侧的Nodal信号而表现出左右模式缺陷。我们将研究Rab23的功能是否需要细胞对节点信号的反应，或者细胞产生作用于其邻居的功能信号。我们还将在胚胎和培养细胞中使用分子方法来验证Rab23控制信号GDF1的分泌或修饰的假设，该信号与Nodal一起作用以适当激活细胞反应。

DESCRIPTION (provided by applicant): The vertebrate body plan is patterned along its left-right axis during development. This ensures that organs are positioned asymmetrically within the body, and that individual organs such as the heart and lungs, adopt an asymmetric structure. Failure of this process during our embryonic development, results in life-threatening disorders such as congenital heart defects. Left-right patterning is governed largely by the asymmetric activity of the Nodal signaling pathway, used for intercellular communication, on the left side of the embryo. Here, we investigate the role of the protein Rab23 in embryonic Nodal signaling. Mouse embryos lacking Rab23 exhibit left-right patterning defects as a result of their failure to activate Nodal signaling on the left side. We will investigate whether Rab23 function is required within cells for their response to Nodal signals or for cells to produce functional signals that act on their neighbors. We will also use molecular methods in the embryo, as well as cells in culture, to test the hypothesis that Rab23 controls the secretion or modification of the signal GDF1, which acts together with Nodal to properly activate cellular responses.