Phenotypic, genetic and molecular analyses of themup-4 gene in Caenorhabditis elegans demonstrate essential functions in maintenance of embryonic muscle position and hypodermal morphogenesis

The mup-4 locus is a member of a class of genes essential for embryonic body wall muscle positioning in Caenorhabditis elegans. Our characterizations demonstrate that mup-4 is essential and support that mup-4 is unique among embryonic muscle position-affecting genes. The mup-4 phenotype is variably expressed and three discrete arrest phenotypes arise in the stage of development during which the worm elongates from a ball of cells to its worm shape. A small proportion of mutants arrest during early stages of elongation, either before elongation has occurred or in mid-elongation, whereas most mup-4 mutants arrest after elongation is essentially complete. Mutants that arrest after elongation display catastrophic displacement of dorsal and ventral muscle cells and a characteristic kinked body shape due to muscle position abnormalities (the Mup phenotype). Intriguingly, genetic mosaic analysis of mup-4 mutants supports that mup-4 gene function is in the hypodermis (epidermis) of the worm, a tissue with which muscle interacts. Furthermore, phenotypic characterizations reveal that mutants have defects in hypodermis integrity and morphology. Genetic and deficiency mapping placed mup-4 into a 100 kb physical interval. Transformation rescue attempts using cosmids and YACs from the mapped interval did not rescue the locus. In this interval we have identified a candidate gene, mrp-1, based on a predicted ORF. This gene is predicted to have motifs consistent with possible functions of mup-4 and is homologous to another C. elegans gene which affects muscle position. We have undertaken approaches to determine if mrp-1 is mup-4. We discuss models for the function of mup-4 in the hypodermis during morphogenesis and in maintenance of muscle position. We also discuss possible function of the candidate gene in our models