My long term goal is to understand morphogenesis at the interface between the cell and tissue levels. Most cells and tissues are polarized. The apical/basal polarity of epithelial cells is a classic example of this. Epithelia are also often polarized in the plane of the tissue and it is this planar polarity that we have studied. Planar polarity is important for convergent extension in the vertebrate embryo, in the arrangement of stereocillia in the inner ear and in the function of many other tissues such as the cilliated epithelia that lines our respiratory tract. Homologs of the genes we discovered our model system have been found to function in vertebrate convergent extension and in the development of the inner ear. Mutations in these genes lead to a failure in neural closure and to defects in hearing and balance. As a model system to study planar polarity we use the fly wing system and a genetic approach. The fly wing is decorated by about 30,000 cuticular hairs all of which point distally resulting in a tissue level planar polarity. Our earlier work led to the discovery of the frizzled pathway, which controlled planar polarity by regulating the subcellular location for the activation of the cytoskeleton to form the hair. Recent work from a number of laboratories has shown that the frizzled pathway genes encode proteins that become asymmetrically localized along the proximal, distal or both sides of wing cells. Our recent work is directed toward understanding how this asymmetric signal is transduced to the cytoskeleton. We propose to continue to study a group of planar polarity effector genes to understand how they function at the cellular level and the molecular genetic basis for their control of cell shape and morphology. ? ? ?
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