Calcium is a ubiquitous intracellular signalling molecule that controls a. wide range of cellular functions. An important means of regulating calcium. signals is through the inositol 1,4,5-trisphosphate (IP3) pathway. IP3 is. produced by the action of the enzyme phospholipase C (PLC). IP3 acts on its. ion-channel receptor, the IP3-receptor, to release Ca2+ from the. endoplasmic reticulum. It has been shown that disruption of this pathway. results in defects in several aspects of embryogenesis in Caenorhabditis. elegans (1,2). Previous work has demonstrated a role for IP3-mediated. calcium signalling in the migration of epidermal cells during embryonic. morphogenesis (1). However, the mechanism by which IP3 production is. regulated in this process is unknown. By surveying the PLC family of C.. elegans using RNAi and mutant strains, we discovered that depletion of PLC-. 1/PLC-epsilon produced substantial embryonic lethality (3). Using the epithelial. cell marker
ajm-1::GFP, to follow the behaviour of epidermal cells, we. found that 96% of these arrested embryos show morphogenetic defects. These. defects include defective ventral migration and aberrant dorsal. intercalation. Using time-lapse confocal microscopy we show that the. migration of the ventral epidermal cells, especially of the leading cells,. is slower and often fails in
plc-1(
tm753) embryos. As a consequence
plc-1. loss of function results in ruptured embryos with a Gex phenotype (gut in. the exterior) and lumpy larvae. Thus PLC-1 is involved in the regulation of. morphogenesis. Genetic studies using gain- and loss-of-function alleles of.
itr-1, the gene encoding the IP3 receptor in C. elegans, demonstrate that. PLC-1 acts through ITR-1. Using RNAi and double mutants to deplete the. other PLCs in a
plc-1 background, we show that PLC-3/PLC-v and EGL-8/PLC-beta. can compensate for reduced PLC-1 activity. Our work places PLC-epsilon into a. pathway controlling epidermal cell migration, thus establishing a novel. role for PLC (3).. 1.Thomas-Virnig CL, Sims PA, Simske JS, Hardin J. (2004) The inositol. 1,4,5-trisphosphate receptor regulates epidermal cell migration in. Caenorhabditis elegans. Curr Biol.14:1882-7.. 2.Walker DS, Gower NJ, Ly S, Bradley GL, Baylis HA. (2002) Regulated. disruption of inositol 1,4,5-trisphosphate signaling in Caenorhabditis. elegans reveals new functions in feeding and embryogenesis. Mol Biol. Cell. 13:1329-37.. 3.Vazquez-Manrique RP, Nagy AI, Legg JC, Bales O AM, Ly S, Baylis HA.. (2008) Phospholipase C-epsilon Regulates Epidermal Morphogenesis in. Caenorhabditis elegans.PLOS Genetics, in press