B09

Wnt-cilia signaling in epithelial polarization and renal development

Funding period: 2021-2025

Project B09

Project Leaders

Prof. Dr. Gislene Pereira

Prof. Dr. Gislene Pereira

 Project Leader B09
Prof. Dr. med. Matias Simons

Prof. Dr. med. Matias Simons

 Project Leader B09

Abstract

Several studies have demonstrated a tight relationship between Wnt signaling and primary cilia. However, the underlying mechanisms as well as the impact on tissue biology remain unanswered. Here, we will combine the expertise of two labs to shed new light on the role of Wnt signaling and ciliogenesis. Using a variety of techniques, including renal organoids and adhesive micropatterns, we want to explore whether cilia and canonical Wnt signaling are linked via a feedback mechanism that simultaneously allows for efficient ciliogenesis and a proper balance of Wnt activation. We further want to test how Wnt and cilia contributes to epithelialization in a critical phase of kidney development.

Project-related Publications

CRISPR/Cas12a-assisted PCR tagging of mammalian genes

Fueller J, Herbst K, Meurer M, Gubicza K, Kurtulmus B, Knopf JD, Kirrmaier D, Buchmuller BC, Pereira G, Lemberg MK, Knop M. J Cell Biol. 2020 Jun 1;219(6):e201910210. doi: 10.1083/jcb.201910210. PMID: 32406907

Learn more
Nek2 kinase displaces distal appendages from the mother centriole prior to mitosis

Viol L, Hata S, Pastor-Peidro A, Neuner A, Murke F, Wuchter P, Ho AD, Giebel B, Pereira G. J Cell Biol. 2020 Mar 2;219(3):e201907136. doi: 10.1083/jcb.201907136. PMID: 32211891

Learn more
Molecular Basis for Autosomal-Dominant Renal Fanconi Syndrome Caused by HNF4A

Marchesin V, Pérez-Martí A, Le Meur G, Pichler R, Grand K, Klootwijk ED, Kesselheim A, Kleta R, Lienkamp S, Simons M. Cell Rep. 2019 Dec 24;29(13):4407-4421.e5. doi: 10.1016/j.celrep.2019.11.066. PMID: 31875549

Learn more
The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis

Kuhns S, Schmidt KN, Reymann J, Gilbert DF, Neuner A, Hub B, Carvalho R, Wiedemann P, Zentgraf H, Erfle H, Klingmüller U, Boutros M, Pereira G. J Cell Biol. 2013 Feb 18;200(4):505-22. doi: 10.1083/jcb.201206013. Epub 2013 Feb 11. PMID: 23400999

Learn more
Drosophila ATP6AP2/VhaPRR functions both as a novel planar cell polarity core protein and a regulator of endosomal trafficking

Hermle T, Guida MC, Beck S, Helmstädter S, Simons M. EMBO J. 2013 Jan 23;32(2):245-59. doi: 10.1038/emboj.2012.323. Epub 2013 Jan 4. PMID: 23292348

Learn more
Cep164 mediates vesicular docking to the mother centriole during early steps of ciliogenesis

Schmidt KN, Kuhns S, Neuner A, Hub B, Zentgraf H, Pereira G. J Cell Biol. 2012 Dec 24;199(7):1083-101. doi: 10.1083/jcb.201202126. Epub 2012 Dec 17. PMID: 23253480

Learn more
Regulation of Frizzled-dependent planar polarity signaling by a V-ATPase subunit

Hermle T, Saltukoglu D, Grünewald J, Walz G, Simons M. Curr Biol. 2010 Jul 27;20(14):1269-76. doi: 10.1016/j.cub.2010.05.057. Epub 2010 Jun 24. PMID: 20579879

Learn more
Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization

Simons M, Gault WJ, Gotthardt D, Rohatgi R, Klein TJ, Shao Y, Lee HJ, Wu AL, Fang Y, Satlin LM, Dow JT, Chen J, Zheng J, Boutros M, Mlodzik M. Nat Cell Biol. 2009 Mar;11(3):286-94. doi: 10.1038/ncb1836. Epub 2009 Feb 22. PMID: 19234454

Learn more
Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways

Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Krönig C, Schermer B, Benzing T, Cabello OA, Jenny A, Mlodzik M, Polok B, Driever W, Obara T, Walz G. Nat Genet. 2005 May;37(5):537-43. doi: 10.1038/ng1552. Epub 2005 Apr 24. PMID: 15852005

Learn more