Editors' ChoiceDevelopment

Planar Cell Polarity Goes Perpendicular

Science Signaling  06 May 2014:
Vol. 7, Issue 324, pp. ec121
DOI: 10.1126/scisignal.2005416

Polarized distribution of signaling molecules followed by asymmetric cell division can restrict the distribution of cell fate determinants to a single daughter cell. The larval skin of the frog is composed mostly of mucus-secreting goblet cells derived from the outer polarized epithelium of the embryonic ectoderm. The skin also contains multiciliated cells, which are derived from a deeper layer of ventral ectoderm cells generated by occasional asymmetric divisions of the outer epithelial cells perpendicular to the epithelial plane. Huang et al. report that the Wnt receptor Lrp6 was enriched in the basolateral domain of the outer epithelial cells and uniformly present on the basal daughters after these cells divided asymmetrically. Wnt signaling through Lrp6 leads to nuclear accumulation of β-catenin and activation of target genes. By endogenous and reporter gene expression criteria, basal cells showed greater Wnt signaling activity than outer epithelial cells. Inhibiting Wnt signaling reduced the number of ciliated cells, and injecting mRNA encoding β-catenin promoted the differentiation of supernumerary multiciliated cells. Signaling through the Frizzled-planar cell polarity (Fz-PCP) pathway, which requires Wnt receptors of the Frizzled family, was required for the asymmetric distribution of Lrp6 in the epithelial cells. Dishevelled (Dvl), a multidomain protein involved in both Wnt-β-catenin and Fz-PCP signaling, colocalized with Lrp6 in the basolateral membrane of outer epithelial cells, and embryos lacking Dvl did not show polarized distribution of Lrp6. Polar localization of Lrp6 required domains in Dvl that mediate PCP signaling, but not a domain required only for Wnt-β-catenin signaling. Morpholino-mediated knockdown of Wnt5a, which has been implicated in PCP, or of Fz7 prevented the polarized distribution of both Lrp6 and Dvl in outer epithelial cells and enrichment of Lrp6 in deep cells. These findings indicate that PCP signaling can influence apicobasal polarity in addition to its well-established role in defining polarity within the plane of the epithelium and demonstrate that PCP and Wnt-β-catenin signaling can cooperate to link cell polarity to fate determination.

Y.-L. Huang, C. Niehrs, Polarized Wnt signaling regulates ectodermal cell fate in Xenopus. Dev. Cell 29, 250–257 (2014). [Online Journal]