Regulation of Asymmetric Division and Cell Fate Determination by C. elegans Wnt-Frizzled Signaling

Wnt-Frizzled signaling is an important regulator of asymmetric cell division that increases cellular diversity. In the nematode Caenorhabditis elegans, mutations in lin-17/Frizzled resulted in supernumerary PVDs, one of the two postdeirid neurons generated by the V5 seam cell lineage. The asymmetric division of the V5.pa, which generated the neuroblast and the glioblast of the postdeirid, was often disrupted in the lin-17 and Wnt mutants. We identified multiple Wnt pathway genes that controlled PVD specification, and showed that Wnts instructed the asymmetry of cell division. Interestingly, expression of lin-26, a C2H2 transcription factor critical for hypodermal and glial cell specification, was significantly diminished in the postdeirid glial lineage of the lin-17 mutant. Reduced activity of lin-26 or lir-1, a lin-26-like gene encoded by the lir-1/lin-26 operon, resulted in supernumerary PVDs and enhanced lin-17 mutant phenotypes. Moreover, combining mutations of lin-17 and another Frizzled, mom-5, resulted in substantial loss of seam cells and extremely aberrant PVD numbers. These results support a model in which Frizzled couples asymmetric cell division to a switch in lin-26/lir-1 transcriptional activity to promote glial or epidermal fates against an otherwise differentiation program towards neurons.