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

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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.