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Harmansa, S.

Publications and source records attributed to Harmansa, S..

5 recordsLinked to original sources

Mechanical regulation of cuboidal-to-squamous epithelial transition in the Drosophila developing wing

Growing tissues are constantly exposed to mechanical stresses that lead to deformations at the cell and tissue scale. In epithelial organs, cells form monolayers whose thickness can change dramatically during development. Here, we address how cell shape changes in the peripodial epithelium of the Drosophila wing disc emerge from the interplay of basement membrane properties with tissue-extrinsic mechanical stress. We show that tissue-extrinsic stress arising from disc proper bending elastically deforms central peripodial cells and induces a cuboidal-to-squamous epithelial transition. In contrast, a rigid basement membrane shields peripheral hinge cells from this bending stress and causes a cuboidal-to-columnar transition. These inverse shape transitions are further amplified by selective shearing of central cells due to coupling via the apical extracellular matrix protein Dumpy. These findings point to a pivotal role of the basement membrane and inter-tissue coupling in the emergence of stress patterns and cell deformations during organ growth.

developmental biology↗

Growth anisotropy of the extracellular matrix drives mechanics in a developing organ

The final size and shape of organs results from volume expansion by growth and shape changes by contractility. Complex morphologies arise from differences in growth rate between tissues. We address here how differential growth drives epithelial thickening and doming during the morphogenesis of the growing Drosophila wing imaginal disc. We report that 3D morphology results from elastic deformation due to differential growth between the epithelial cell layer and its enveloping extracellular matrix (ECM). Furthermore, the ECM envelope exhibits differential growth anisotropy (i.e. anisotropic expansion in 3D), growing in-plane on one side, but out of plane on the other side. The elasticity, anisotropy and morphogenesis is fully captured by a mechanical bilayer model. Moreover, differential expression of the Matrix metalloproteinase MMP2 controls growth anisotropy of the two ECM layers. This study shows that the ECM is a controllable mechanical constraint whose intrinsic growth anisotropy directs tissue morphogenesis in a developing organ.

developmental biology↗

Self-organized Toll-8/Cirl GPCR asymmetry drives planar polarized cell contractility

During development, 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 G protein-coupled receptor (GPCR) signaling whereas Myosin-II polarity requires patterned expression of several Toll receptors. How Toll receptors polarizes 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 via a novel binding partner, 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 a novel cell surface protein complex Toll-8/Cirl self-organizes to generate local asymmetric interfaces essential for planar polarization of contractile interfaces.

developmental biology↗

A nanobody-based toolset to investigate the role of protein localization and dispersal in Drosophila

Investigating the role of protein localization is crucial to understand protein function in cells or tissues. However, in many cases the role of different subcellular fractions of given proteins along the apical-basal axis of polarized cells has not been investigated in vivo, partially due to lack of suitable tools. Here, we present the GrabFP system, a nanobody-based toolbox to modify the localization and the dispersal of GFP-tagged proteins along the apical-basal axis of polarized cells. We show that the GrabFP system is an effective and easy-to-implement tool to mislocalize cytosolic and transmembrane GFP-tagged proteins and thereby functionally investigate protein localization along the apical-basal axis. We use the GrabFP system as a tool to study the extracellular dispersal of the Decapentaplegic (Dpp) protein and show that the Dpp gradient forming in the lateral plane of the Drosophila wing disc epithelium is essential for patterning of the wing imaginal disc.

developmental biology↗

Myosin II activity is not required for Drosophila tracheal branching morphogenesis

The Drosophila tracheal system consists of an interconnected network of monolayered epithelial tubes that ensures oxygen transport in the larval and adult body. During tracheal dorsal branch (DB) development, individual DBs elongate as a cluster of cells, led by tip cells at the front and trailing cells in the rear. Branch elongation is accompanied by extensive cell intercalation and cell lengthening of the trailing stalk cells. While cell intercalation is governed by Myosin II (MyoII)-dependent forces during tissue elongation in the Drosophila embryo leading to germ-band extension, it remained unclear whether MyoII plays a similar active role during tracheal branch elongation and intercalation. Here, we use a nanobody-based approach to selectively knock-down MyoII in tracheal cells. Our data shows that despite the depletion of MyoII function, tip cells migration and stalk cell intercalation (SCI) proceeds at a normal rate. Therefore, our data confirms a model in which DB elongation and SCI in the trachea occurs as a consequence of tip cell migration, which produces the necessary forces for the branching process.\n\nSummary statementBranch elongation during Drosophila tracheal development mechanistically resembles MyoII-independent collective cell migration; tensile forces resulting from tip cell migration are reduced by cell elongation and passive stalk cell intercalation.\n\nAbbreviations

developmental biology↗