Sci. Signal., 17 January 2012
Development Wnt Signaling and Cilia Intertwined
Annalisa M. VanHook
Science Signaling, AAAS, Washington, DC 20005, USA
Most mammalian cells produce a single nonmotile (primary) cilium, which acts as a sensory organelle and signaling center. In contrast, motile cilia are produced in large numbers by some types of cells that are exposed to fluid flow, such as cells of the airways and reproductive tract. Proteins such as basal body components and intraflagellar transport proteins are required for building cilia, but the upstream mechanisms controlling ciliogenesis are not well understood. Caron et al. report that the canonical Wnt/β-catenin pathway is required for ciliogenesis in Kupffers vesicle (KV), a fluid-filled sac lined with cells that each bear a single motile cilium, and required for proper establishment of left-right (LR) asymmetry in the developing zebrafish embryo. Wnt signaling was specifically required in KV cells for proper LR asymmetry, and reducing Wnt signaling by expressing an inhibitor of signaling or morpholinos targeting pathway components resulted in fewer, shorter cilia with impaired motility in KV compared with controls. Reducing Wnt signaling specifically in KV cells caused a decrease in the expression of foxj1a, which encodes a transcription factor that is necessary and sufficient for ciliogenesis, and expression of foxj1a rescued the KV cilia defects in embryos with reduced Wnt signaling. Genetic epistasis experiments indicated that fibroblast growth factor (FGF) signaling, which had previously been shown to be required for ciliogenesis, acted upstream of Wnt signaling in ciliogenesis. Activation of Wnt signaling causes the stabilization and nuclear translocation of β-catenin, which cooperates with the Lef and Tcf transcription factors to activate the expression of target genes. The authors identified possible Lef/Tcf binding sites in the foxj1a promoter and demonstrated that these were required for foxj1a expression in KV cells, suggesting that Wnt signaling directly stimulates expression of this master regulator of ciliogenesis. Wnt signaling was also required for ciliogenesis in the otic vesicles and pronephric ducts, indicating that Wnt signaling may be generally required for ciliogenesis. It has been reported that primary cilia influence Wnt signaling in some cell types and that Wnt/planar cell polarity (PCP) signaling influences cilia function, and now it appears that canonical Wnt/β-catenin signaling may also affect the assembly and function of cilia.
Citation: A. M. VanHook, Wnt Signaling and Cilia Intertwined. Sci. Signal. 5, ec22 (2012).
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