Formation of polarized contractile interfaces by self-organized Toll-8/Cirl GPCR asymmetry

Jules Lavalou, Qiyan Mao, Stefan Harmansa, Stephen Kerridge, Annemarie C Lellouch, Jean-Marc Philippe, Stephane Audebert, Luc Camoin, Thomas Lecuit

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)
6 Downloads (Pure)

Abstract

Interfaces between cells with distinct genetic identities elicit signals to organize local cell behaviors driving tissue morphogenesis. The Drosophila embryonic axis extension requires planar polarized enrichment of myosin-II powering oriented cell intercalations. Myosin-II levels are quantitatively controlled by GPCR signaling, whereas myosin-II polarity requires patterned expression of several Toll receptors. How Toll receptors polarize myosin-II and how this involves GPCRs remain unknown. Here, we report that differential expression of a single Toll receptor, Toll-8, polarizes myosin-II through binding to the adhesion GPCR Cirl/latrophilin. Asymmetric expression of Cirl is sufficient to enrich myosin-II, and Cirl localization is asymmetric at Toll-8 expression boundaries. Exploring the process dynamically, we reveal that Toll-8 and Cirl exhibit mutually dependent planar polarity in response to quantitative differences in Toll-8 expression between neighboring cells. Collectively, we propose that the cell surface protein complex Toll-8/Cirl self-organizes to generate local asymmetric interfaces essential for planar polarization of contractility.

Original languageEnglish
Pages (from-to)1574-1588.e7
JournalDevelopmental Cell
Volume56
Issue number11
Early online date30 Apr 2021
DOIs
Publication statusPublished - 7 Jun 2021

Bibliographical note

Funding Information:
We thank all members of the Lecuit team, B. Aigouy (IBDM, France) for stimulating discussions during the course of this project, the IBDM imaging facility for microscopy assistance, FlyBase for maintaining curated databases and the Bloomington Stock Center for providing fly stocks. We thank T. Langenhan and N. Scholz (Leipzig, Germany) for sharing information about Cirl and fly reagents, and for stimulating discussions. We thank B. Aigouy (IBDM, France) and P. Villoutreix (Centuri, France) for developing the method for quantifying clone smoothness in wing discs. We thank B. Habermann (IBDM, France) for her valuable guidance on performing pairwise alignment between Toll-8 and FLRTs. We are grateful to M. Ludwig (Birmingham, UK), P.F. Lenne (IBDM, France), E. Wieschaus (Princeton, USA), A. Martin (MIT, USA), R. Karess (IJM, France), G. Jim?nez (IBMB, Spain) and T. Gregor (Pasteur Institute, France) for the gift of flies and vectors. This work was supported by grants from the European Research Council, European Union (Biomecamorph no. 323027) and the Ligue Nationale Contre le Cancer, France (Equipe Labellis?e, 2018). J.L. was supported by the Fondation Bettencourt Schueller, France and the Coll?ge de France. S.H. was supported by an EMBO Long-Term Fellowship (EMBO ALTF 217-2017) and by a Centuri Postdoctoral Fellowship. The Marseille proteomics (IBiSA) is supported by Institut Paoli-Calmettes (IPC) and Cancerop?le PACA. Proteomic analyses were done using the mass spectrometry facility of Marseille proteomics (marseille-proteomique.univ-amu.fr) supported by IBISA (Infrastructures Biologie Sant? et Agronomie), Plateforme Technologique Aix-Marseille, the Canc?rop?le PACA, the Provence-Alpes-C?te d'Azur R?gion, the Institut Paoli-Calmettes and the Centre de Recherche en Canc?rologie de Marseille. We acknowledge the France-BioImaging infrastructure supported by the French National Research Agency (ANR?10?INBS-04-01, Investments for the future). J.L. Q.M. and T.L. conceived the project. Q.M. J.L. and S.K. performed experiments in embryos, Q.M. analyzed them. J.L. performed all the experiments and data analysis in fixed wing discs. S.H. performed and analyzed live experiments in wing discs and quantified data in Figures 5 and 6. Q.M. and A.L. prepared the samples for the mass spectrometry, which was done and analyzed by S.A. and L.C. J.-M.P. designed and generated the molecular constructs. J.L. Q.M. and T.L. wrote the manuscript, and all authors made comments. The authors declare no competing interests.

Funding Information:
We thank all members of the Lecuit team, B. Aigouy (IBDM, France) for stimulating discussions during the course of this project, the IBDM imaging facility for microscopy assistance, FlyBase for maintaining curated databases and the Bloomington Stock Center for providing fly stocks. We thank T. Langenhan and N. Scholz (Leipzig, Germany) for sharing information about Cirl and fly reagents, and for stimulating discussions. We thank B. Aigouy (IBDM, France) and P. Villoutreix (Centuri, France) for developing the method for quantifying clone smoothness in wing discs. We thank B. Habermann (IBDM, France) for her valuable guidance on performing pairwise alignment between Toll-8 and FLRTs. We are grateful to M. Ludwig (Birmingham, UK), P.F. Lenne (IBDM, France), E. Wieschaus (Princeton, USA), A. Martin (MIT, USA), R. Karess (IJM, France), G. Jiménez (IBMB, Spain) and T. Gregor (Pasteur Institute, France) for the gift of flies and vectors. This work was supported by grants from the European Research Council , European Union (Biomecamorph no. 323027 ) and the Ligue Nationale Contre le Cancer , France (Equipe Labellisée, 2018). J.L. was supported by the Fondation Bettencourt Schueller , France and the Collège de France . S.H. was supported by an EMBO Long-Term Fellowship (EMBO ALTF 217-2017) and by a Centuri Postdoctoral Fellowship. The Marseille proteomics (IBiSA) is supported by Institut Paoli-Calmettes (IPC) and Canceropôle PACA. Proteomic analyses were done using the mass spectrometry facility of Marseille proteomics (marseille-proteomique.univ-amu.fr) supported by IBISA (Infrastructures Biologie Santé et Agronomie), Plateforme Technologique Aix-Marseille, the Cancéropôle PACA, the Provence-Alpes-Côte d'Azur Région, the Institut Paoli-Calmettes and the Centre de Recherche en Cancérologie de Marseille. We acknowledge the France-BioImaging infrastructure supported by the French National Research Agency ( ANR–10–INBS-04-01 , Investments for the future).

Publisher Copyright:
© 2021 The Authors

Fingerprint

Dive into the research topics of 'Formation of polarized contractile interfaces by self-organized Toll-8/Cirl GPCR asymmetry'. Together they form a unique fingerprint.

Cite this