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.

组织稳态涉及消除异常细胞以避免模式和功能受损。尽管在上皮组织中通过细胞竞争进行的质量控制已得到充分研究，但尚不清楚间充质群体中是否以及如何调节体内平衡。在这里，我们证明集体迁移的果蝇肌肉前体利用成纤维细胞生长因子（FGF）和骨形态发生蛋白（BMP）信号传导通过失巢凋亡（一种响应基质脱粘附的细胞死亡形式）促进体内平衡。细胞死亡基因头部复旧缺陷的细胞周期调节表达是导致尾部内脏中胚层（CVM）失巢凋亡的原因。分泌的 BMP 配体通过内脏中胚层特异性cdc25/string增强子驱动细胞周期进程，以同步集体增殖以及失去底物来源 FGF 的细胞凋亡。BMP 依赖性细胞周期进程的扰动足以赋予失巢凋亡对错误迁移细胞的抵抗力，从而促进其他组织的侵袭。这种 BMP 门控细胞周期检查点定义了间充质集体迁移过程中的质量控制机制。