BMP-gated cell-cycle progression drives anoikis during mesenchymal collective migration

Abstract

Tissue homeostasis involves the elimination of abnormal cells to avoid compromised patterning and function. Although quality control through cell competition is well studied in epithelial tissues, it is unknown if and how homeostasis is regulated in mesenchymal collectives. Here, we demonstrate that collectively migrating Drosophila muscle precursors utilize both fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) signaling to promote homeostasis via anoikis, a form of cell death in response to substrate de-adhesion. Cell-cycle-regulated expression of the cell death gene head involution defective is responsible for caudal visceral mesoderm (CVM) anoikis. The secreted BMP ligand drives cell-cycle progression via a visceral mesoderm-specific cdc25/string enhancer to synchronize collective proliferation, as well as apoptosis of cells that have lost access to substrate-derived FGF. Perturbation of BMP-dependent cell-cycle progression is sufficient to confer anoikis resistance to mismigrating cells and thus facilitate invasion of other tissues. This BMP-gated cell-cycle checkpoint defines a quality control mechanism during mesenchymal collective migration.