Trpml controls actomyosin contractility and couples migration to phagocytosis in fly macrophages

Edwards-Jorquera, Sandra; Bosveld, Floris; Bellaı̈che, Yohanns; Lennon-Duménil, Ana-María; Glavic, Álvaro

doi:10.1083/jcb.201905228

“…Similarly, lysosomal storage disorders that lead to vacuolation are associated with perturbed immune cell migration in patient-derived cells [66][67][68] and experimental models 69 . Sequestration of regulators of both phagocytosis and motility, such as the lysosomal Trp channel Trpml (the fly homologue of TRPML1/MCOLN1) 70 further understand how apoptotic cells regulate changes in macrophage behaviour in vivo, such as their migration and phagocytic capacities, especially since initial specification of macrophages does not appear compromised in this background and repo plays no direct functional role in these cells.…”

Section: Discussionmentioning

confidence: 99%

Overexposure to apoptosis via disrupted glial specification perturbs Drosophila macrophage function and reveals roles of the CNS during injury

Armitage

¹

,

Roddie

²

,

Evans

³

2020

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Apoptotic cell clearance by phagocytes is a fundamental process during development, homeostasis and the resolution of inflammation. However, the demands placed on phagocytic cells such as macrophages by this process, and the limitations these interactions impose on subsequent cellular behaviours are not yet clear. Here, we seek to understand how apoptotic cells affect macrophage function in the context of a genetically tractable Drosophila model in which macrophages encounter excessive amounts of apoptotic cells. Loss of the glial-specific transcription factor Repo prevents glia from contributing to apoptotic cell clearance in the developing embryo. We show that this leads to the challenge of macrophages with large numbers of apoptotic cells in vivo. As a consequence, macrophages become highly vacuolated with cleared apoptotic cells, and their developmental dispersal and migration is perturbed. We also show that the requirement to deal with excess apoptosis caused by a loss of repo function leads to impaired inflammatory responses to injury. However, in contrast to migratory phenotypes, defects in wound responses cannot be rescued by preventing apoptosis from occurring within a repo mutant background. In investigating the underlying cause of these impaired inflammatory responses, we demonstrate that wound-induced calcium waves propagate into surrounding tissues, including neurons and glia of the ventral nerve cord, which exhibit striking calcium waves on wounding, revealing a previously unanticipated contribution of these cells during responses to injury. Taken together, these results demonstrate important insights into macrophage biology and how repo mutants can be used to study macrophage-apoptotic cell interactions in the fly embryo. Furthermore, this work shows how these multipurpose cells can be 'overtasked' to the detriment of their other functions, alongside providing new insights into which cells govern macrophage responses to injury in vivo.

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“…To better visualize the basal surface of the neck epidermis, an ex vivo live or fixed imaging approach was adapted from 71 . Upon removal of the pupal case, pupae were glued on their dorsal side to a 20 mm glass bottom microwell dish (MatTek Life Sciences) using heptane glue 72 .…”

Section: Methodsmentioning

confidence: 99%

Homeotic compartment curvature and tension control spatiotemporal folding dynamics

Villedieu

¹

,

Alpar

²

,

Gaugué

³

et al. 2023

Self Cite

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Shape is a conspicuous and fundamental property of biological systems entailing the function of organs and tissues. While much emphasis has been put on how tissue tension and mechanical properties drive shape changes, whether and how a given tissue geometry influences subsequent morphogenesis remains poorly characterized. Here, we explored how curvature, a key descriptor of tissue geometry, impinges on the dynamics of epithelial tissue invagination. We found that the morphogenesis of the fold separating the adult Drosophila head and thorax segments is driven by the invagination of the Deformed (Dfd) homeotic compartment. Dfd controls invagination by modulating actomyosin organization and in-plane epithelial tension via the Tollo and Dystroglycan receptors. By experimentally introducing curvature heterogeneity within the homeotic compartment, we established that a curved tissue geometry converts the Dfd-dependent in-plane tension into an inward force driving folding. Accordingly, the interplay between in-plane tension and tissue curvature quantitatively explains the spatiotemporal folding dynamics. Collectively, our work highlights how genetic patterning and tissue geometry provide a simple design principle driving folding morphogenesis during development.

show abstract

“…To better visualize the basal surface of neck epidermis, an ex vivo live or fixed imaging approach was adapted from 70 . Upon removal of the pupal case, pupae were glued on their dorsal side to a 20 mm glass bottom microwell dish (MatTek Life Sciences) using heptane glue 71 .…”

Section: Ex Vivo Imaging Of the Basal Surface Of The Pupal Dorsal Epi...mentioning

confidence: 99%

Homeotic compartment curvature and tension control spatiotemporal folding dynamics

Villedieu

¹

,

Alpar

²

,

Gaugué

³

et al. 2022

Preprint

Self Cite

0

View full text Add to dashboard Cite

Shape is a conspicuous and fundamental property of biological systems entailing the function of organs and tissues. While much emphasis has been put on how tissue tension and mechanical properties drive shape changes, whether and how a given tissue geometry influences subsequent morphogenesis remains poorly characterized. Here, we explored how curvature, a key descriptor of tissue geometry, impinges on the dynamics of epithelial tissue invagination. We found that the morphogenesis of the fold separating the adult Drosophila head and thorax segments is driven by the invagination of the Deformed (Dfd) homeotic compartment. Dfd controls invagination by modulating actomyosin organization and in-plane epithelial tension via the Tollo and Dystroglycan receptors. By experimentally introducing curvature heterogeneity within the homeotic compartment, we established that a curved tissue geometry converts the Dfd-dependent in-plane tension into an inward force driving folding. Accordingly, the interplay between in-plane tension and tissue curvature quantitatively explains the spatiotemporal folding dynamics. Collectively, our work highlights how genetic patterning and tissue geometry provide a simple design principle driving folding morphogenesis during development.

show abstract

Trpml controls actomyosin contractility and couples migration to phagocytosis in fly macrophages

Cited by 10 publications

References 65 publications

Overexposure to apoptosis via disrupted glial specification perturbs Drosophila macrophage function and reveals roles of the CNS during injury

Overexposure to apoptosis via disrupted glial specification perturbs Drosophila macrophage function and reveals roles of the CNS during injury

Homeotic compartment curvature and tension control spatiotemporal folding dynamics

Homeotic compartment curvature and tension control spatiotemporal folding dynamics

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