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.
