The large-scale remodeling of the C. elegans larval male tail provides an ideal opportunity to study the integration of the sex determination pathway with cellular differentiation and morphogenesis programs. Despite the apparent dissimilarity between sex determination pathways across phyla, proteins containing a divergent Zn-finger motif called the DM domain have been found to play key roles as sex determination effectors in animals as diverse as worms, flies and fish. Thus DM-domain factors may be thought of as sexual analogs of Hox genes, specifying sexual information in the way that Hox genes specify positional information.
We have recently identified a novel C. elegans DM-domain gene,
dmd-3, that is expressed male-specifically in the tail tip hypodermal cells
hyp8-
hyp11 during morphogenesis.
dmd-3 mutant males exhibit a striking defect in male tail morphogenesis such that the blunt-ended male tail is partially transformed to a tapered hermaphrodite-like tail. In addition to this morphological defect, the fusion of the
hyp8-
hyp11 cells that characterizes normal tail remodeling fails to occur in
dmd-3 males. Consistent with this, we have found that
dmd-3 is required for the normal male-specific tail-tip expression of EFF-1, a critical regulator of developmental cell fusion.
The expression pattern of
dmd-3 reporters suggests that sexual, temporal and spatial inputs converge at the level of
dmd-3 transcription. Spatial regulation of
dmd-3 in the tail tip requires TLP-1, a transcription factor necessary for tail tip morphogenesis. We are examining the roles of the heterochronic and sex-determination pathways in regulating the temporal and sexual specificity of
dmd-3.
The phenotype of
dmd-3 males partially overlaps with, yet is distinct from, the mutant phenotypes of
mab-3 and
mab-23, two other DM domain genes. We have found that
mab-3 strongly enhances the tail retraction defect of
dmd-3 males, indicating that these DM domain proteins act in concert to coordinate male tail morphogenesis. Our findings suggest that
dmd-3 is a critical regulator of male tail morphogenesis, linking multiple upstream inputs to downstream effectors that control tail tip cell fusion and retraction.