The successful execution of many biological functions requires physical linkage between cell layers of different types. In C. elegans, a link between the bodywall muscle and the hypodermis is required for locomotion. This linkage is mediated in part by hemidesmosomes (HDs) found in regions of the hypodermis adjacent to muscle. We are interested in understanding the signals required to establish and maintain the correct spatial relationship between the muscle and the HDs. The localization of a protein we have named myotactin suggests it may participate in muscle-hypodermal communication. Myotactin is expressed by dorsal and ventral hypodermal cells and in adults colocalizes with HDs. However, during part of embryogenesis, the position of myotactin mirrors that of the contractile apparatus in the forming muscle. The predicted amino acid sequence encodes a novel transmembrane protein with at least 32 fibronectin type III repeats extracellularly and a unique cytoplasmic tail, consistent with a role in muscle-hypodermal linkage. We isolated a myotactin mutation (
st456), which we believe to be lose of function, and showed it to be allelic to
let-805(
s2764) (D. Baillie). All aspects of the phenotype examined, and discussed below, can be rescued by the introduction of the wild type myotactin sequence suggesting
st456 is in fact a myotactin mutation. Furthermore, all aspects of the phenotype can be mimicked by RNA-mediated interference using double stranded RNA homologous to 2 different regions of the myotactin gene. This suggests
st456 and
s2764 are both loss of function. Myotactin appears to be involved in muscle cell adhesion as well as in maintaining the connection between muscle and HDs. Both
let-805 alleles, like known muscle (pat class) and muscle collagen mutants, arrest elongation at the two-fold stage, display little or no movement, and die before hatching. Examination of
let-805 mutants shows the muscle forms as in wild type, but the muscle cells detach from the hypodermis when contractions begin, consistent with a role in muscle cell adhesion. A second aspect of the
let-805 phenotype is delocalization of HDs. Initially, the HDs appear to form and localize as in wild type. However, after the muscle cells detach, HDs are seen all through dorsal and ventral hypodermis. Interestingly, we have found this phenotype in some pat mutants, where myotactin itself remains associated with muscle, indicating myotactin and HD localization have been uncoupled. We suggest a signaling event requiring muscle function links myotactin to HDs, restricting their position to regions of the hypodermis adjacent to muscle.