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Phenotypes

Mouse phenotype:

abnormal auditory brainstem response

Subcellular localization

Ciliary associated gene, Vesicles

Functional category

• Signaling (Hedgehog
• GPCRs
• ion channels)
• Ciliary assembly/disassembly

Function

We here show in the mucociliary epidermis of X. tropicalis embryos that motile cilia transduce a ciliary Wnt signal that is distinct from canonical β-catenin signaling. Instead, it engages a Wnt-Gsk3-Ppp1r11-Pp1 signaling axis. Mucociliary Wnt signaling is essential for ciliogenesis and it engages Lrp6 co-receptors that localize to cilia via a VxP ciliary targeting sequence.Ppp1r11 morphants expectedly showed greatly reduced ppp1r11 mRNA levels and injection of human ppp1r11 mRNA effectively rescued cilia morphology, both results confirming morpholino specificity (Supplementary Fig. 3k–m). By immunoblot analysis, co-transfection of GSK3 increased phospho-serine and phospho-threonine levels in immuno-precipitated Ppp1r11 while BIO treatment reversed this effect, corroborating that Ppp1r11 is subject to GSK3 phosphorylation (Fig. 2i). Co-injection of ppp1r11 DNA in ccny/l1 morphants rescued their cilia defect, confirming that Ppp1r11 acts downstream of Ccny/l1 as in our model (Fig. 2j, k). In addition, treatment of ppp1r11 morphants with the PP1 inhibitor OA partially restored cilia morphology, verifying that ppp1r11 regulates MCC cilia via PP1 (Supplementary Fig. 3n, o). Collectively, the results support that an evolutionary conserved ciliary Wnt ┫Pp1 signaling axis promotes ciliogenesis in motile cilia (Fig. 2a, schematic)(36878953).