Prickle and Van Gogh Function in the Mouse

Studies in the fruitfly Drosophila melanogaster have shown that the PCP proteins Van Gogh (Vang; also known as Strabismus, a four-pass transmembrane protein), and Prickle (a conserved, prenylated LIM domain protein), play essential roles in generating asymmetric subcellular localization of Fz and Dsh. These localizations are, in turn, required to produce cellular asymmetries. These proteins have also been implicated in PCP signaling in vertebrates. Van Gogh is required for planar polarization of the cochlear hair cells in the inner ear, and both Van Gogh and Prickle are required polarize cells which then undergo stereotypical movements known as convergence and extension, which elongate the axis of the developing embryo during gastrulation.

Mice and humans each have two close homologs of Prickle and Van Gogh. In addition, two more distantly related members of the prickle gene family have been identified. To better understand the contributions of these gene families to vertebrate development, we are studying them in the mouse by examining expression patterns, generating conditional knock-out and overexpression strains, and a variety of other assays. These studies will emphasize their roles in neural tube closure, inner ear, respiratory epithelium and cerebellar development. Some of these studies are being carried out in collaboration with Matthew Scott in the Department of Developmental Biology at Stanford.

The in vivo studies are being complemented with cell culture experiments in which PCP is reconstituted, both to further understand mechanisms, and to learn to engineer PCP patterns by controlling the PCP machinery.