Genetic integration of semaphorin and ephrin pathways regulating epidermal morphogenesis in Caenorhabditis elegans

Consistent with the function of plexins as specific receptors for semaphorins in other organisms, an allele of plexin-2/plx-2 was identified in this screen. Additional alleles of plx-2, including a null allele have been isolated in order to genetically characterize plx-2 function in C. elegans. Our genetic analysis shows that plx-2 functions in the same genetic pathway as mab-20 as expected for a receptor. Surprisingly, mab-20 also signals in a pathway that is parallel and partially redundant to plx-2. We propose that MAB-20 signals through a functionally redundant, non-plexin receptor(s). In addition, we show that this novel pathway is dependent on both mab-20 and efn-4 function demonstrating an integrated semaphorin/ephrin signaling control. Newly identified erf-1 and erf-2 were also shown to signal through this mab-20-dependent efn-4 pathway in a redundant manner with plx-2 as shown by a synthetic ray fusion defect (synMab).The restricted expression of PLX-2 confers the cell-specific function of ubiquitously expressed MAB-20 in development. We present both a genetic and cellular model for mab-20-dependent guidance of pocket cell migration during ventral enclosure and show that Eph receptor vab-1 functions in parallel to plx-2 to position a PLX-2 expressing neuroblast domain. This PLX-2 neuroblast domain appears to function as a restrictive substratum for the guidance and ventral midline cell matching of the overlying migrating pocket cells.Semaphorins and ephrins are two conserved families of proteins identified as repulsive cues in axon guidance. In C. elegans, semaphorin-2a/mab-20 and ephrin-4/efn-4 regulate ventral enclosure and the sorting of sensory ray precursor cells during male tail morphogenesis. Several erf (e&barbelow;nhancer of r&barbelow;ay f&barbelow;usion) mutations were identified in an enhancer screen for the ray fusion defect of a weak allele of mab-20 and may represent new genes in the semaphorin pathway.The work completed in my first Ph.D. project prior to the work described in this thesis is briefly outlined in Appendix A---Characterization of check-point induced arrest and apoptosis in the zebrafish embryo.