Transforming Growth Factor β/activin signalling induces epithelial cell flattening during Drosophila oogenesis
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Abstract:
Although the regulation of epithelial morphogenesis is essential for the formation of tissues and organs in multicellular organisms, little is known about how signalling pathways control cell shape changes in space and time. In the Drosophila ovarian epithelium, the transition from a cuboidal to a squamous shape is accompanied by a wave of cell flattening and by the ordered remodelling of E-cadherin-based adherens junctions. We show that activation of the TGFβ pathway is crucial to determine the timing, the degree and the dynamic of cell flattening. Within these cells, TGFβ signalling controls cell-autonomously the formation of Actin filament and the localisation of activated Myosin II, indicating that internal forces are generated and used to remodel AJ and to promote cytoskeleton rearrangement. Our results also reveal that TGFβ signalling controls Notch activity and that its functions are partly executed through Notch. Thus, we demonstrate that the cells that undergo the cuboidal-to-squamous transition produce active cell-shaping mechanisms, rather than passively flattening in response to a global force generated by the growth of the underlying cells. Thus, our work on TGFβ signalling provides new insights into the mechanisms through which signal transduction cascades orchestrate cell shape changes to generate proper organ structure.Keywords:
Adherens junction
Adherens junction
Nectin
Cell–cell interaction
Beta-catenin
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Adherens junction
VE-cadherin
Nectin
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Adherens junction
Cleavage (geology)
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Capillary endothelial cells express Vascular Endothelial (VE)‐ and Neural (N)‐cadherin, with overlapping functions. VE‐cadherin forms homotypic adhesion between endothelial cells whereas N‐cadherin forms heterotypic adhesion with the surrounding pericytes in capillary endothelia. Endothelial specific deletions of Cdh2 (N‐cadherin) or Cdh5 (VE‐cadherin) in mice demonstrated poorly formed leaky capillaries and in utero death at E9.5 due to defective angiogenesis. These findings raise the question of whether N‐ and VE‐cadherin function independently or whether N‐cadherin activated signaling regulates the assembly of VE‐cadherin and thereby the formation of adherens junctions. We investigated the role of N‐cadherin in the formation of VE‐cadherin junctions using mouse genetic models and identifying N‐cadherin signaling pathways in endothelial monolayers. We show that N‐cadherin functions by interacting with the RhoGEF Trio to activate the RhoGTPases Rac1 and RhoA in nascent adherens junctions, inducing the recruitment of VE‐cadherin. This N‐cadherin activated signaling pathway is essential for maximal VE‐cadherin assembly and the formation of the endothelial junctional barrier. Support or Funding Information Supported by NIH grant R01 HL103922 to Y.A.K.; AHA AWARD 16PRE27260230 to K.K. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Adherens junction
VE-cadherin
Vascular permeability
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Adherens junction
Cleavage (geology)
VE-cadherin
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Adherens junction
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The mechanism that coordinates different adhesion receptors is poorly understood. We investigated this mechanism by focusing on the nectin-2 and E-cadherin adherens junction receptors. Cadherin is not required for the basic process of nectin junction formation since nectin-2 forms junctions in cadherin-deficient A431D cells. Formation of nectin junctions in these cells, however, becomes regulated by cadherin as soon as E-cadherin is reconstituted. E-cadherin recruits nectin-2 into adherens junctions, where both proteins form distinct but tightly associated clusters. Live-cell imaging showed that the appearance of cadherin clusters often precedes that of nectin clusters at sites of junction assembly. Inactivation of cadherin clustering by different strategies concomitantly suppresses the formation of nectin clusters. Furthermore, cadherin significantly increases the stability of nectin clusters, thereby making them resistant to the BC-12 antibody, which targets the nectin-2 adhesion interface. By testing different cadherin-α-catenin chimeras, we showed that the recruitment of nectin into chimera junctions is mediated by the actin-binding domain of α-catenin. Our data suggests that cadherin regulates-assembly of nectin junctions through α-catenin-induced remodeling of the actin cytoskeleton around the cadherin clusters.
Adherens junction
Nectin
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Adherens junction
Cell–cell interaction
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