Developmental control of cell polarity in vertebrate embryos.

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A long-term goal of our lab is to understand the molecular basis of cell polarity and tissue morphogenesis in vertebrate embryos. Our focus here is on the Planar Cell Polarity (PCP) signaling cascade, a molecular mechanism that governs both the formation of cilia and cell movements called convergent extension. Cilia are microtubule-based projections of the cell with important roles in a wide range of human pathologies. For example, the directed fluid flow generated by ciliated cells is crucial for the function of the nervous system, the kidney, the reproductive systems, and the airway. Such “ciliopathies” include cystic kidney diseases, obesity syndromes, infertility, situs abnormalities, and morphological defects on the central nervous system. Convergent extension cell movements are required for neural tube closure in vertebrates, including humans. This proposal will examine the role of the PCP protein, Fritz, in ciliogenesis and convergent extension. During ciliogenesis, we will ask what role Fritz plays in polyglutamylation of microtubules and in the organization of the septin cytoskeleton. During convergent extension, we will ask how Fritz controls cell behaviors, including membrane protrusive activity and centrosomal positioning. Together, these experiments will help us to understand how PCP signaling influences such diverse cellular processes as convergent extension and ciliogenesis.