Semin Cell Dev Biol
June 1, 2015;
Spatial and temporal aspects of Wnt signaling and planar cell polarity during vertebrate embryonic development.
Wnt signaling pathways act at multiple locations and developmental stages to specify cell fate and polarity in vertebrate embryos. A long-standing question is how the same molecular machinery can be reused to produce different outcomes. The canonical Wnt/β-catenin branch modulates target gene transcription to specify cell fates along the dorsoventral and anteroposterior embryonic axes. By contrast, the Wnt/planar cell polarity (PCP) branch is responsible for cell polarization along main body axes, which coordinates morphogenetic cell behaviors during gastrulation and neurulation. Whereas both cell fate and cell polarity are modulated by spatially- and temporally-restricted Wnt activity, the downstream signaling mechanisms are very diverse. This review highlights recent progress in the understanding of Wnt-dependent molecular events leading to the establishment of PCP and linking it to early morphogenetic processes.
Semin Cell Dev Biol
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Fig. 1. Two major Wnt pathway branches.The canonical Wnt/-catenin pathway antagonizes the -catenin destruction complex, consisting of Axin, GSK3 and APC to promote target gene transcription. By contrast,the Wnt/PCP pathway is thought to involve Frizzled/Dishevelled signaling to locally activate RhoA, ROCK and Myosin II and, at the same time, precludes the recruitment ofVangl2/Prickle to the same membrane subdomain. Roles of the vertebrate PCP proteins Fuzzy, Inturned and Diversin in PCP are unclear. Besides the mutually antagonisticinteractions inside the cell, PCP is coordinated by the positive feedback between the Frizzled/Dishevelled complex and the Vangl2/Prickle complex across the cell junction.Two neighboring epithelial cells are shown.
Fig. 2. Anteroposterior and mediolateral PCP in the Xenopus neural plate.En face views of the Xenopus neural plate shown for stage 14–16 embryos. Left, immunostaining for Vangl2 and ZO1 reveals anterior accumulation of Vangl2 in neural midline cells (arrows). Inset shows whole embryo view with indicated anteroposterior (A-P) and mediolateral (M-L) axes. Right, the middle area of the neural plate exhibits mediolateral planar polarity of the cells mosaically expressing GFP-Rab11 (green) and RFP-Diversin (red puncta) that are enriched at medial domains of cells in the lateral neural plate. Arrows mark cell polarization towards the midline (dotted line).
Regulation of morphogenetic behaviors by Wnt/PCP signaling.
The Wnt/PCP pathway modulates actomyosin dynamics and vesicular trafficking to control mediolateral and radial cell intercalations, apical constriction, collective and individual cell migration and oriented cell division. Together, these cell behaviors ensure proper vertebrate neural tube closure.