Wnt signaling pathways control many aspects of animal development including cell type specification, cell migration and spindle orientation. In C. elegans, a Wnt pathway regulates the development of two neuroectodermal precursors called P11 and P12. In normal development, the posterior cell adopts the P12 cell fate in response to Wnt (and EGF signals) while the anterior cell does not and instead adopts the P11 cell fate. One difference between these two cell fates is that P11 produces a large hypodermal cell called P11.p whereas P12 produces a small hypodermal cell called P12.pa. These cell types P11.p and P12.pa are commonly used as markers for the P11 and P12 fates. We are investigating the mechanisms of Wnt signaling in P12 development. Prior studies have shown that
lin-44/Wnt,
lin-17/Frizzled and
bar-1/beta-catenin function in P12 specification. We have found that a constitutively active form of
bar-1 (deltaN-BAR-1) causes P11 to P12 transformations. Together, these results suggest
bar-1 is necessary and sufficient for P12 specification. Because beta-catenins typically activate the transcription factor TCF-1, this predicts that
pop-1, the sole TCF-1 homolog of C. elegans, will also act in P12 specification. Consistent with this prediction, we have found that the
pop-1 hypomorph
hu9 causes a P12 to P11 transformation. Surprisingly, however, we find that
pop-1 RNAi causes the opposite effect resulting in a loss of P11.p and the presence of an extra P12.pa-like cell. This apparent P11 to P12 cell fate transformation suggests that POP-1 has an additional function in P11 specification. Epistasis experiments indicate that this latter function of
pop-1 is independent of
bar-1. We find that multiple Wnts act in P12 specification.
lin-44/Wnt
(n1792) and
egl-20/Wnt
(n585) double mutants display an enhanced rate of P12 to P11 transformations. Other possible roles for additional Wnts and Wnt receptors in P11/P12 development will be discussed.