aPKC regulates apical constriction to prevent tissue rupture in the Drosophila follicular epithelium

Osswald, Mariana; Barros-Carvalho, André; Carmo, Ana M.; Loyer, Nicolas; Grácio, Patrícia; Sunkel, Cláudio E.; Homem, Catarina C.F.; Januschke, Jens; Morais-de-Sá, Eurico

doi:10.1016/j.cub.2022.08.063

Cited by 17 publications

(13 citation statements)

References 90 publications

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“…We also examined another potential mechanism by which Rap1 might regulate balanced contractility. Work from the Morais-de-Sa lab ( Osswald et al. , 2022 ), published while our manuscript was being revised, revealed that reducing the activity of the apical polarity regulator aPKC led to unbalanced contractility in the Drosophila follicle cell epithelium, with hyperconstriction of cells neighboring those bordering mitotic cells and subsequent gaps in the epithelium.…”

Section: Resultsmentioning

confidence: 99%

Rap1 regulates apical contractility to allow embryonic morphogenesis without tissue disruption and acts in part via Canoe-independent mechanisms

Perez-Vale

Yow

Gurley

et al. 2023

MBoC

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Embryonic morphogenesis is powered by dramatic changes in cell shape and arrangement, driven by the cytoskeleton and its connections to adherens junctions. This requires robust linkage, allowing morphogenesis without disrupting tissue integrity. The small GTPase Rap1 is a key regulator of cell adhesion, controlling both cadherin-mediated and integrin-mediated processes. We have defined multiple roles in morphogenesis for one Rap1 effector, Canoe/Afadin, which ensures robust junction-cytoskeletal linkage. We now ask what mechanisms regulate Canoe and other junction-cytoskeletal linkers during Drosophila morphogenesis, defining roles for Rap1 and one of its guanine nucleotide exchange factor (GEF) regulators, Dizzy. Rap1 uses Canoe as one effector, regulating junctional planar polarity. However, Rap1 has additional roles in junctional protein localization and balanced apical constriction—in its absence, Bazooka/Par3 localization is fragmented, and cells next to mitotic cells apically constrict and invaginate, disrupting epidermal integrity. In contrast, the GEF Dizzy has phenotypes similar to but slightly less severe than Canoe loss, suggesting this GEF regulates Rap1 action via Canoe. Taken together, these data reveal that Rap1 is a crucial regulator of morphogenesis, likely acting in parallel via Canoe and other effectors, and that different Rap1 GEFs regulate distinct functions of Rap1.

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Section: Resultsmentioning

confidence: 99%

Rap1 regulates apical contractility to allow embryonic morphogenesis without tissue disruption and acts in part via Canoe-independent mechanisms

Perez-Vale

Yow

Gurley

et al. 2023

MBoC

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“…Thus, cell-cell adhesions may be coupled to cell viability during tissue growth during oogenesis. Indeed, this period of dramatic tissue growth places extra strain on the epithelial follicle cells (Osswald et al, 2022), which could result in fewer cells surviving. Another major role for Rap1 was in promoting survival of the mature polar cells.…”

Section: Discussionmentioning

confidence: 99%

“…While we did not observe Myo-II localization defects when Rap1 was inhibited, the requirement for α-Catenin indicates that linkage to the actomyosin cytoskeleton is critical for epithelial cell and tissue shapes. Atypical Protein Kinase C (aPKC) promotes an optimal level of actomyosin to maintain an intact and organized follicle cell epithelium (Osswald et al, 2022). Indeed, acute loss of aPKC causes the follicle cell layer to apically constrict and rupture, due to growth of the egg chamber.…”

Section: Rap1 Maintains Cell and Tissue Shapes By Modulating Adherens...mentioning

confidence: 99%

“…Since the adherens junction-cytoskeleton linker α-Catenin also supports proper adhesion and α-Catenin RNAi resulted in increased caspase activity during oogenesis, this may indicate a role for cell-cell adhesions in cell viability during tissue growth during Drosophila oogenesis. This period of dramatic tissue growth likely places extra strain on the epithelial follicle cells (Osswald et al, 2022). Thus, having proper cell-cell adhesions is critical for epithelial integrity and cell survival during tissue morphogenesis.…”

Section: Rap1 Promotes Follicle Cell and Polar Cell Survival During O...mentioning

confidence: 99%

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Rap1 promotes epithelial integrity and cell viability in a growing tissue

Messer

McDonald

2022

Preprint

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Having intact epithelial tissues is critical for embryonic development and adult homeostasis. How epithelia respond to damaging insults or tissue growth while still maintaining intercellular connections and barrier integrity during development is poorly understood. The conserved small GTPase Rap1 is critical for establishing cell polarity and regulating cadherin-catenin cell junctions. Here, we identified a new role for Rap1 in maintaining epithelial integrity and tissue shape of a growing tissue, theDrosophilaegg chamber during oogenesis. Loss of Rap1 activity disrupted the follicle cell epithelium and shape of egg chambers. While Rap1 did not control the localization of non-muscle myosin II (Myo-II), it was required for the apical enrichment of E-Cadherin in some cells. Both Myo-II and the adherens junction-cytoskeletal linker protein α-Catenin were required for normal egg chamber shape. Further, we found that Rap1 promoted epithelial cell survival. Follicle cells deficient for Rap1 had increased caspase activity and underwent apoptosis. Loss of Myo-II did not affect cell survival, though loss of α-Catenin resulted in a mild increase in cells undergoing apoptosis. Blocking the apoptotic cascade failed to rescue the cell shape defects caused by Rap1inhibition. One consequence of increased cell death caused by Rap1 inhibition was the preferential loss of the polar cells, which later in development led to fewer cells forming a properly migrating border cell cluster. Our results thus indicate dual roles for Rap1 in controlling epithelial morphogenesis and cell survival of a growing tissue during development.

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“…Pupae were collected and mounted for dorsal thorax, wing or histoblast live imaging as described previously (Bardet et al, 2013; Bosveld et al, 2012; Pinheiro et al, 2017). Dissected egg chambers were imaged live in culture medium (Schneider’s medium, Sigma-Aldrich) supplemented with 10% Fetal bovine serum (Thermo Fisher) and 200 μg/uL insulin (Sigma- Aldrich) as previously described (Osswald et al, 2022). For imaging of fixed tissue, egg chambers were fixed in 4% paraformaldehyde solution in PBT (PBS + 0.2% Tween 20, Sigma- Aldrich) for 20 min, washed with PBT and mounted with Vectashield with DAPI (Vector Laboratories).…”

Section: Methods Detailsmentioning

confidence: 99%

Systematic characterization ofDrosophilaRhoGEF/GAP localizations uncovers regulators of mechanosensing and junction formation during epithelial cell division

Pietro

Osswald

Heras

et al. 2022

Preprint

Self Cite

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Cell proliferation is central to epithelial tissue development, repair and homeostasis. During cell division, small RhoGTPases control both actomyosin dynamics and cell-cell junction remodelling to faithfully segregate the duplicated genome while maintaining tissue polarity and integrity. To decipher the mechanisms of RhoGTPases spatiotemporal regulation during epithelial cell division, we generated a transgenic fluorescently tagged library for Drosophila Rho Guanine exchange factors (GEF) and GTPase activating proteins (GAP), and systematically characterized their endogenous distributions by time-lapse microscopy. Thereby, we unveiled candidate regulators of the interplay between actomyosin and junctional dynamics during epithelial cell division. Building on these findings, we uncovered that during cytokinesis, Cysts and RhoGEF4 play sequential roles in mechanosensing and de novo junction formation, respectively. We foresee that the RhoGEF/GAP library will be a key resource to understand the broad range of biological processes regulated by RhoGTPases.

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aPKC regulates apical constriction to prevent tissue rupture in the Drosophila follicular epithelium

Cited by 17 publications

References 90 publications

Rap1 regulates apical contractility to allow embryonic morphogenesis without tissue disruption and acts in part via Canoe-independent mechanisms

Rap1 regulates apical contractility to allow embryonic morphogenesis without tissue disruption and acts in part via Canoe-independent mechanisms

Rap1 promotes epithelial integrity and cell viability in a growing tissue

Systematic characterization ofDrosophilaRhoGEF/GAP localizations uncovers regulators of mechanosensing and junction formation during epithelial cell division

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