The Caenorhabditis elegans Distal-less ortholog ceh-43 is required for development of the anterior hypodermis

Homeobox genes of the Distal-less (Dll) class are expressed in developing appendages as well as in the central nervous system in invertebrates and vertebrates. Mutant analyses in mice and Drosophila have implicated these genes in outgrowth of structures, cell adhesion, cell migration, and cell fate decisions. We have investigated the expression and function of ceh-43, the Dll ortholog from the nematode Caenorhabditis elegans, by using gfp reporter constructs and double-stranded RNA-mediated interference (RNAi). Our results show that, as in the fly, the C. elegans Dll ortholog seems to play a role in cell adhesion. An antibody against the butterfly Distal-less homeodomain stains the nervous system of C. elegans embryos (Panganiban et al. [1997] Proc Natl Acad Sci USA. 94:5162-5166). GFP expression under the control of the ceh-43 promoter looks similar, although strong expression is primarily confined to the head hypodermis and to neuronal support cells. ceh43(RNAi) results in 100% lethality at embryonic or early larval stages. At the beginning of morphogenesis, ceh-43(RNAi) embryos start to lose cells through a hole in the head hypodermis. They either rupture anteriorly as elongation proceeds, or they elongate normally to threefold egg length with the pharynx not connected to the mouth. Elongated ceh-43(RNAi) animals die before or soon after hatching with a fluid-filled pseudocoel and large vacuoles. These phenotypes suggest a role for ceh-43 in development of adhesive properties in the head hypodermis that connects the epithelia of the skin and the digestive tract. Furthermore, possible defects in the excretory system may result at least in part from a requirement for ceh-43 in the CAN neurons where ceh-43::gfp is also expressed. (C) 2001 Wiley-Liss, Inc.