Calmodulin (CaM), a small calcium binding protein, is a key mediator of numerous calcium induced changes in cellular activity. Its ligands include enzymes, cytoskeletal proteins and ion channels, identified in large part by biochemical and cell biological approaches. Little is known about the functions of CaM-like genes. Thus far it has been difficult to assess the function of CaM genetically, because of the maternal supply in Drosophila and the presence of at least three nonallelic genes in vertebrates. Here we have used RNAi to analyse the functional importance of the single calmodulin gene (
cmd-1) and the four calmodulin-like genes (
cal-1 to
cal-4) present in C. elegans. We find that RNAi leads to embryonic lethality for the calmodulin gene
cmd-1 and an uncoordinated phenotype for the
cal-4 gene. By detailed analysis of the
cmd-1 RNAi embryos with the 4D-Microscope system we observed disturbed morphogenesis, aberrant cell migration patterns and a striking hyperproliferation of cells in the treated embryos. Normal apoptosis is suppressed in some instances, but in addition ectopic cell deaths occur and engulfment of cell corpses is inhibited. RNAi also allows several genes to be inactivated simultaneously. The triple RNAi approach for the
cal-1,
cal-2 and
cal-3 genes gives rise to a complex phenotype while individual inactivations do not lead to a scorable phenotype.