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Pour maintenir l'organisation et la polarité du tissu épithélial, de nouvelles jonctions cellulaires ont besoin de se former lors de la division cellulaire. Pour comprendre les mécanismes de formation de la jonction durant la cytokinèse, nous avons exploré dans les tissus épithéliaux de la Drosophile, la formation des jonctions septées tricellulaires (TCJs), critique à la fois dans la fonction de barrière tissulaire, dans l'homéostasie des cellules souches, ainsi que dans l'orientation du fuseau mitotique. Durant les dernières étapes de la constriction de l'anneau contractile, les membranes des deux cellules filles et des cellules voisines localisées sous la jonction adhérente (JA) restent enchevêtrées dans une structure à 4 cellules apposée au corps intermédiaire. Les constituants protéiques de la jonction septée, Discs-large (Dlg) et Neuroglian (Nrg), ainsi que les composants de la TCJ, Gliotactin (Gli) et Anakonda (Aka), s'accumulent dans cette structure à 4 cellules. Par la suite, la descente basale du corps intermédiaire est corrélée au détachement des membranes des cellules voisines, au désengagement des cellules filles de leurs voisines, et à la formation de TCJs matures. Le détachement des cellules voisines du corps intermédiaire est indépendant de l'abscision. Au contraire, la perte de la fonction Gli ou Aka empêche le détachement entre les cellules filles-voisines et le mouvement du corps intermédiaire. Ainsi, nous proposons que les protéines de la TCJ contrôlent une étape additionnelle de la cytokinèse, nécessaire au désengagement des cellules filles et de leurs voisines durant la cytokinèse épithéliale. / To maintain epithelial tissue organisation and polarity, new cell-cell junctions need to be formed upon cell division. To understand the mechanisms of junction formation during cytokinesis, we explored in Drosophila epithelial tissues, the de novo formation of tricellular septate junctions (TCJs), which are critical to tissue barrier function, stem cell homeostasis and mitotic spindle orientation. During the final stages of cytokinetic ring constriction, the membranes of the two daughter cells and of the neighbouring cells located below the adherens junction (AJ) remain entangled in a 4-cell structure apposed to the midbody. Protein constituents of the septate junction Discs-large (Dlg) and Neuroglian (Nrg) and the components of the TCJ Gliotactin (Gli) and Anakonda (Aka) accumulate in this 4-cell structure. Subsequently, a basal descent of the midbody correlates with the detachment of the neighbouring cell membranes, disengagement of the daughter cells from their neighbours and the formation of mature TCJs. The detachment of the neighbouring cells from the midbody is independent of abscission. On the contrary, the loss of Gli or Aka function prevents the resolution of the connection between the daughter-neighbour cells and the midbody movement. Altogether, we propose that TCJ proteins control an additional step of cytokinesis necessary for the disentanglement of the daughter cells and their neighbours during epithelial cytokinesis.

The work presented in this thesis provides insights into the Drosophila smooth septate junction complex Ssk-Mesh that regulates ISC proliferation and tissue homeostasis in addition to the well-known barrier function in the epithelial integrity. With CRISPR-generated tag knockin alleles of Ssk and Mesh, I characterized the intracellular expression pattern of Ssk and Mesh. Ssk and Mesh had low but detectable expression in punctate format in the cytoplasm of enteroblasts (EBs). The protein expression profile of Ssk and Mesh correlated with their ability to regulate the ISC proliferation even though the septate junctions in EBs had not fully formed. Along with further differentiation into mature enterocytes (ECs), Ssk and Mesh gradually localized to the epithelial apical domain, where they coordinated with other junction proteins, such as Tsp2A and Coracle, to form the septate junction. RNAi-conducted genetic assays and mutant clonal analyses by knockout mutant alleles of Ssk and mesh further revealed that Ssk and Mesh restricted the activity of the transcription coactivator Yki, which governs the production of the cytokine Upd3 along the EB-EC differentiation lineage in adult midgut. Loss of Ssk or Mesh activated Yki to elevate the upd3 expression and thereby to induce the robust ISC proliferation non-autonomously. Although the total number of EBs in midgut is much fewer than that of ECs, surprisingly, knockdown Ssk or mesh in EBs resulted in a comparable upd3 upregulation and ISC proliferation as knockdown their expression in ECs. Leaky midgut caused by knockdown of Ssk or mesh in ECs activated the stress-responding mechanisms to repair the damaged intestinal epithelium, and was eventually associated with death of animals. The reduction of Ssk and Mesh in EBs displayed much milder gut leakage and lower lethality further confirmed that Ssk and Mesh in the two distinct cell types had their own roles in governing ISC proliferation.