During C. elegans embryonic development, cell-cell signaling is used at multiple stages to provide positional cues within the embryo. At the four cell stage, the EMS blastomere requires a polarity inducing signal from its neighboring blastomere P2. Loss of this signal results in EMS dividing symmetrically into two nearly identical daughters, both giving rise to mesodermal tissues at the expense of the intestine. This phenotype has been termed Mom for more of mesoderm. The opposite phenotype is observed in
pop-1 mutants where both daughters of EMS adopt E-like fates. We used antisense microinjection to ask if components of the conserved WNT signaling pathway which is implicated in tissue and cellular polarity in many other systems might play a role in the early C. elegans embryo. We found that three of our previously identified Mom mutations,
mom-2,
mom-4 and
mom-5 mapped to genetic locations that coincide with Wnt components. We confirmed the identities of
mom-2 (Wnt/signal) and
mom-5 (Frizzled/receptor) first by "antisensing" the corresponding clones, to confirm the Mom phenotype, and then by sequencing our alleles. The
mom-4 gene has been less co-operative, even though it coincides with the location of a gene related to another player in the Wnt signaling, APC (Adenomatous Polyposis Coli), and even though this clone induces a beautiful Mom phenotype, we have, AS YET, been unable identify molecular lesions in this APC-like gene in any of our
mom-4 alleles. One other component for which we have a phenotype but no mutations is a gene we call
wrm-1, (worm armadillo motif-1). While all of the other components when assayed either by antisense or as actual mutations are incompletely penetrant for the Mom phenotype (making gut 50% to 80% of the time), we find that
wrm-1 antisense gives a fully penetrant Mom phenotype. Interestingly, double mutants between APC-like and
mom-2 (Wnt) also result in a fully penetrant Mom phenotype. This observation is consistent with a model in which the WRM-1 protein integrates two separate signals required for the asymmetric division of the EMS blastomere. We speculate that one of these signals is interpreted by APC-like and may reflect pre-existing polarity cues that were induced at fertilization. In addition to their defects in EMS development, Mom mutations also exhibit defects in AB differentiation and cleavage patterns, raising the possiblity that Wnt signaling plays a global role in defining early embryonic polarity.