Cellular morphogenesis requires that signals instructing cell shape change be translated into changes in the structure and dynamics of the actin cytoskeleton. The actin-binding protein UNC-115 acts downstream of Rac GTPase signaling during axon development. While UNC-115 is required for some axon development events, it acts redundantly with Rac GTPases in other events. Furthermore,
unc-115 is expressed in tissues not affected by
unc-115 mutation, including the hypodermis and the pharynx. These observations suggest that UNC-115 acts redundantly with other actin-binding proteins in axon development and possibly in the development of other tissues (e.g. pharynx). To identify genes that act redundantly with
unc-115, we initiated a screen for
unc-115 synthetic lethal mutations using an array that rescues
unc-115 loss of function. To date, we have identified four mutations that are synthetic lethal with
unc-115 from ~2000 haploid genomes screened. These mutations define at least three genes. Three mutations (
ky535,
lq18 and
lq19) displayed a grossly normal phenotype when isolated alone but were slow-growing and had reduced brood sizes. Double mutants of these three mutations with
unc-115(
mn481) arrested as early L1 larvae that were severly uncoordinated but displayed no gross morphological defects. In contrast,
lq15 animals alone were slightly uncoordinated and displayed abnormal hypodermal bulges and constrictions resembling Vab mutants. Furthermore,
lq15;
unc-115(
mn481) double mutants arrested as embryos or L1 larvae with severe morphological defects. Thus, different classes of mutations that are synthetic with
unc-115 have been identified, possibly refelecting the differing redundant roles of
unc-115 in different tissues.While
ky535 alone has a grossly normal phenotype, we found that the gonad architecture of
ky535 mutants is perturbed. In the wild-type gonad, the germline nuclei are arranged regularly under the sheath cells, forming a single layer of nuclei around the mostly germ nucleus-free rachis. In
ky535 mutants, germ nuclei are often seen in the area of the central rachis, sometimes forming lines of nuclei that cross the rachis to the other side. Further anatomical studies are underway to determine the cellular basis of this germ nucleus defect. Preliminary mapping and RNAi experiments indicate that
ky535 might affect a gene encoding a known actin-binding protein. Possibly, this actin-binding protein acts redundantly with UNC-115 for viability and is required for proper germ cell architecture.