The Formin Frl functions in Planar Cell Polarity Signaling in Drosophila. Andreas Jenny¹, Saw-Myat Maung¹, Gretchen Dollar¹, Cathie Pfleger². 1) Dept Molec & Dev Biol, Albert Einstein Col Med, Bronx, NY; 2) Department of Oncological Sciences Mount Sinai School of Medicine, New York, NY.

   The non-canonical Fz/Planar cell polarity (PCP) pathway regulates establishment of polarity within the plane of an epithelium to generate diversity of cell fates, asymmetric, but highly aligned structures (e.g. stereocilia in the inner), or to orchestrate the directional migration of cells during convergent extension during vertebrate gastrulation. In Drosophila, PCP is essential to orient actin wing hairs and to polarize the ommatidia in the eye by coordinating the movement of groups of photoreceptors during ommatidial rotation. Thus, common themes in PCP dependent processes are cytoskeletal rearrangements and cell migration processes. PCP is governed by Wnt signals through Fz to elicit nuclear responses and cytoskeletal changes mediated by Rho Kinase (Rok). Loss of rok causes ommatidial rotation and neural tube defects in flies and fish, respectively, yet how Rok is regulated and its targets during PCP remain largely unknown. In a genome wide screen to identify novel Rok substrates we identified the formin Frl, the single fly FMNL (Formin related in Leukocytes/ Formin-like). Formins catalyze actin polymerization and are thus compelling candidates to regulate cytoskeletal changes downstream of Rok. To investigate Frl function, we took a loss of function approach and found that knock-down of or mutations in frl cause PCP defects in the eye, consistent with a role for Frl in PCP signaling. Furthermore, dominant negative frl genetically interacts with cdc42 and rhoA, suggesting that Frl integrates signals from different Rho family GTPases. We are addressing how Frl acts inPCP signaling. In particular, we test if Frl acts together with Daam, a formin that was previously shown to link RhoA to Dsh during PCP signaling in Xenopus, but has no PCP phenotype in flies. Our findings bring us closer to a better understanding of how the PCP signal is transduced to the cytoskeleton and suggest that FMNL homologs might function during PCP signaling in vertebrates.