{"id":7889,"date":"2021-03-18T11:17:55","date_gmt":"2021-03-18T11:17:55","guid":{"rendered":"http:\/\/www.sci.muni.cz\/ofiz\/?p=7889"},"modified":"2021-03-18T11:17:56","modified_gmt":"2021-03-18T11:17:56","slug":"primary-cilia-formation-does-not-rely-on-wnt-%ce%b2-catenin-signaling-2","status":"publish","type":"post","link":"https:\/\/ueb1.sci.muni.cz\/ofiz\/en\/primary-cilia-formation-does-not-rely-on-wnt-%ce%b2-catenin-signaling-2\/","title":{"rendered":"Primary Cilia Formation Does Not Rely on WNT\/\u03b2-Catenin Signaling"},"content":{"rendered":"\n
Abstract:<\/strong><\/h5>\n

Primary cilia act as crucial regulators of embryo development and tissue homeostasis. They are instrumental for modulation of several signaling pathways, including Hedgehog, WNT, and TGF-\u03b2.<\/p>\n

However, gaps exist in our understanding of how cilia formation and function is regulated. Recent work has implicated WNT\/\u03b2-catenin signaling pathway in the regulation of ciliogenesis, yet the results are conflicting. One model suggests that WNT\/\u03b2-catenin signaling negatively regulates cilia formation, possibly via effects on cell cycle. In contrast, second model proposes a positive role of WNT\/\u03b2-catenin signaling on cilia formation, mediated by the re-arrangement of centriolar satellites in response to phosphorylation of the key component of WNT\/\u03b2-catenin pathway, \u03b2-catenin.<\/p>\n

To clarify these discrepancies, we investigated possible regulation of primary cilia by the WNT\/\u03b2-catenin pathway in cell lines (RPE-1, NIH3T3, and HEK293) commonly used to study ciliogenesis. We used WNT3a to activate or LGK974 to block the pathway, and examined initiation of ciliogenesis, cilium length, and percentage of ciliated cells.<\/p>\n

We show that the treatment by WNT3a has no- or lesser inhibitory effect on cilia formation. Importantly, the inhibition of secretion of endogenous WNT ligands using LGK974 blocks WNT signaling but does not affect ciliogenesis. Finally, using knock-out cells for key WNT pathway components, namely DVL1\/2\/3, LRP5\/6, or AXIN1\/2 we show that neither activation nor deactivation of the WNT\/\u03b2-catenin pathway affects the process of ciliogenesis.<\/p>\n

These results suggest that WNT\/\u03b2-catenin-mediated signaling is not generally required for efficient cilia formation. In fact, activation of the WNT\/\u03b2-catenin pathway in some systems seems to moderately suppress ciliogenesis.<\/p>\n\n\n\n

Front Cell Dev Biol. 2021 Feb 26;9:623753.doi: 10.3389\/fcell.2021.623753. eCollection 2021.<\/em> <\/a><\/p>\n\n\n\n

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WNT3a does not promote ciliogenesis or cilia length. (A) <\/strong>Experimental scheme of WNT3a treatment experiment. Cells were seeded and grown for 24 h, then starved for additional 48 h. A 2 h treatment (RPE-1) by WNT3a is indicated in blue, 24 h treatment is indicated in orange (RPE-1 and NIH3T3). (B) Western blot analysis of 2 h WNT3a treatment of RPE-1. The treatment leads to LRP6 shift and increased LRP5\/6 phosphorylation, DVL2 phosphorylation and upshift, and accumulation of ABC.<\/figcaption><\/figure>\n\n\n\n
Authors:<\/strong><\/h5>\n

Ondrej Bernatik 1<\/sup>, Petra Paclikova 2<\/sup>, Anna Kotrbova 2<\/sup>, Vitezslav Bryja 2<\/sup><\/strong>, Lukas Cajanek 1<\/sup><\/p>\n

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  • 1<\/sup> Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czechia.<\/li>\n
  • 2<\/sup> Section of Animal Physiology and Immunology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia.<\/li>\n<\/ul>\n\n\n