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Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration

2018; Elsevier BV; Volume: 45; Issue: 3 Linguagem: Inglês

10.1016/j.devcel.2018.04.002

1878-1551

Aparna Ratheesh, Julia Biebl, Jana Vesela, Michael Smutny, Ekaterina Papusheva, Simon Frederik Gabriel Krens, Walter A. Kaufmann, Attila Gyoergy, Alessandra Maria Casano, Daria E. Siekhaus,

Developmental Biology and Gene Regulation

Highlights•Macrophages invade into the germband between the ectoderm and mesoderm•The Drosophila TNF, Eiger, is released from a neighboring tissue onto the germband•Eiger acts via Grindelwald and Crumbs complex component Patj to lower active Myosin•Eiger thus reduces apical tension in the ectoderm to facilitate invasive migrationSummaryMigrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm. Interestingly, the genetic pathway governing these mechanical shifts acts downstream of the only known tumor necrosis factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald. Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated tight junction protein). We therefore elucidate a distinct molecular pathway that controls tissue tension and demonstrate the importance of such regulation for invasive migration in vivo.