Mutations in the C. elegans Eph receptor tyrosine kinase, VAB-1, and the ephrins, EFN-1/VAB-2 and EFN-4/MAB-26, cause defects in neural and epidermal morphogenesis. These defects are incompletely penetrant, suggesting that other pathways may function in parallel. To identify components of such parallel pathways we investigated whether
vab-1 mutations displayed synthetic lethality with other morphogenetic mutants. A mutation in a C. elegans receptor tyrosine phosphatase,
ptp-3(
op147) , previously known as
ptp-1 , causes mild morphogenetic defects similar to those of weak
vab-1 alleles. We have found that
ptp-3(
op147) synergizes with
vab-1 mutations.
ptp-3(
op147) also synergizes with mutations in ephrin genes
efn-1/vab-2 and
efn-4/mab-26 suggesting that PTP-3 may have redundant functions with Eph signaling to regulate morphogenesis.
ptp-3 does not display genetic interaction with other RTK mutants or morphogenetic mutants tested. PTP-3 is most similar to LAR-like receptor protein tyrosine phosphatases. We have found that the
ptp-3 locus encodes two isoforms, PTP-3A and PTP-3B. PTP-3A contains 3 Ig-like domains, 8 fibronectin type III repeats, and two tandem cytoplasmic phosphatase domains. PTP-3B contains only 4 FNIII repeats and the two phosphatase domains. PTP-3 isoforms are expressed in many tissues in early embryogenesis, and later become localized to neuronal processes and to epithelial adherens junctions. Interestingly, mutations that specifically delete the PTP-3A isoform (isolated by the C. elegans Gene Knockout Consortium) display wild type morphogenesis and do not synergize with Eph signaling mutants. PTP-3A and PTP-3B may have overlapping functions in morphogenesis and loss of one or the other may not cause significant defects (the
op147 mutation affects both isoforms). We have analyzed the phenotypes of
ptp-3 single mutants and
vab-1 ptp-3 double mutants using 4D microscopy.
ptp-3 mutants have gastrulation and ventral closure defects similar to those of Eph signaling mutants.
vab-1 ptp-3 double mutants show the same defects, only at a higher frequency. Our data suggest that PTP-3 and Eph signaling function redundantly. We are currently using tissue specific promoters to ask whether PTP-3 and VAB-1 function redundantly in the same tissues.