Epithelial tissues are composed of a sheet of adherent cells and are present in all metazoans. Their broad function is to compartmentalize tissues and enable the regulated exchange of nutrients and waste between the internal and external environments. To accomplish this function, cells require a specific organization: an apico-basal polarity that provides directionality and intercellular adhesion mediated by adherens junctions that hold cells together. How the epithelia architecture is initiated and maintained remains to be fully elucidated. Adherens junctions and the polarity proteins are functionally linked, as a loss of the main component of AJs: E-cadherin leads to a loss of apico-basal polarity, while disturbing apico-basal polarity results in a re-localization of E-Cadherin. Therefore is challenging to study either pathway in isolation.During my thesis I explored the role of Crumbs, a polarity protein, in the regulation of E-Cadherin in both AJ maturation and maintenance. During maturation of AJs in Drosophila embryo, I demonstrated for the first time by using quantitative high-resolution microscopy PALM that Crumbs regulates E-Cadherin clusters size and their homogenous distribution along the junction. In conclusion, my thesis work provides the first dissection of polarity proteins in E-Cadherin regulation apart from polarity pathways. / Epithelial tissues are composed of a sheet of adherent cells and are present in all metazoans. Their broad function is to compartmentalize tissues and enable the regulated exchange of nutrients and waste between the internal and external environments. To accomplish this function, cells require a specific organization: an apico-basal polarity that provides directionality and intercellular adhesion mediated by adherens junctions that hold cells together. How the epithelia architecture is initiated and maintained remains to be fully elucidated. Adherens junctions and the polarity proteins are functionally linked, as a loss of the main component of AJs: E-cadherin leads to a loss of apico-basal polarity, while disturbing apico-basal polarity results in a re-localization of E-Cadherin. Therefore is challenging to study either pathway in isolation.During my thesis I explored the role of Crumbs, a polarity protein, in the regulation of E-Cadherin in both AJ maturation and maintenance. During maturation of AJs in Drosophila embryo, I demonstrated for the first time by using quantitative high-resolution microscopy PALM that Crumbs regulates E-Cadherin clusters size and their homogenous distribution along the junction. In conclusion, my thesis work provides the first dissection of polarity proteins in E-Cadherin regulation apart from polarity pathways.

Les tissus épithéliaux sont des couches de cellules adhérentes qui servent de barrières entre différents compartiments morphologiques et procurent un transport directionnel de molécules. L’action coopérative de plusieurs déterminants de la polarité gouverne l’identité et la morphogenèse spécifiques de ces domaines : 1) le cytosquelette d’actomyosine, 2) les jonctions adhérentes (AJs) basées sur la E-cadhérine et 3) les complexes de polarité conservés au cours de l’évolution. Une perte de l’adhérence via la DE-cadhérine (DE-Cad) conduit à des défauts de polarité apico-basale, tandis que la localisation apicale de DE-Cad nécessite les protéines de polarité Crumbs (Crb) et Bazooka (Baz) (L’homologue de Par3 chez la mouche). Notablement, DE-Cad forme des amas qui co-localisent partiellement avec les amas de Baz, génèrent l’adhésion intercellulaire et transmettent la tension. Les mécanismes impliqués dans le contrôle de la taille, le nombre, la répartition et la dynamique des amas de DE-Cad restent peu connus.J’ai étudié le rôle de Crumbs et Baz dans la régulation de la distribution fine de DE-Cad. J’ai montré que Crb contrôle la distribution macroscopique de DE-Cad, au moins, partiellement via Baz. En générant des mutations de Baz sur des sites régulateurs variés grâce à de la transgenèse spécifique de site et en utilisant de la microscopie en temps réel quantitative, j’ai montré que Crb agit via le domaine d’oligomérisation CR1 et le site Ser980 de Baz afin d’ajuster les niveaux de DE-Cad. Remarquablement, j’ai aussi révélé que le domaine d’oligomérisation de Baz est inutile à la formation d’amas Baz-DE-Cad et j’ai caractérisé la réciprocité de l’interaction DE-Cad-Baz. / Epithelia are sheets of adherent cells that serve as barriers between distinct morphological compartments and provide directed transport of molecules.. The cooperative action of several polarity determinants governs the proper identity and morphogenesis of these domains: 1) actomyosin cytoskeleton; 2) E-Cadherin-based adherens junctions (AJs) and 3) evolutionarily conserved polarity complexes.A loss of DE-cadherin (DE-Cad) adhesion leads to apico-basal polarity defects, while the apical localization of DE-Cad requires the polarity proteins Crumbs (Crb) and Bazooka (Baz) (Par3 homolog in fly). Notably, DE-Cad builds clusters that display a certain degree of colocalization with the clusters of Baz, provide intercellular adhesion and transmit tension.I have addressed the role of Crumbs and Baz in the regulation of DE-Cad fine distribution. I demonstrated that Crb controls DE-cad macroscopic distribution, at least, partially via Baz. By generating Baz mutants on various regulatory sites using site-specific transgenesis and quantitative live-imaging microscopy, I showed that Crb acts via CR1 oligomerization domain and Ser980 site of Baz to adjust DE-Cad levels. I also revealed that Baz oligomerization domain is dispensable for Baz-DE-Cad clusters formation and characterized the reciprocity of DE-Cad-Baz crosstalk.