BMP-gated cell-cycle progression drives anoikis during mesenchymal collective migration.
BMP-gated cell-cycle progression drives anoikis during mesenchymal collective migration.
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DOI：
10.1016/j.devcel.2022.05.017
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发表时间：
2022-07-25
影响因子：
11.8
通讯作者：
Stathopoulos, Angelike
中科院分区：
文献类型：
--
作者：
Macabenta, Frank;Sun, Hsuan-Te;Stathopoulos, Angelike
组织稳态包括消除异常细胞以避免受损的模式和功能。虽然通过细胞竞争的质量控制在上皮组织中得到了很好的研究，但尚不清楚间充质集体中是否以及如何调节稳态。在这里，我们证明，集体迁移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，以促进体内平衡通过失巢凋亡，一种形式的细胞死亡，在响应基板去粘附。细胞周期调控的细胞死亡基因头部退化缺陷的表达负责尾部内脏中胚层（CVM）失巢凋亡。分泌的BMP配体通过内脏中胚层特异性cdc 25/string增强子驱动细胞周期进程，以同步集体增殖，以及失去基质来源的FGF的细胞凋亡。BMP依赖的细胞周期进程的扰动足以赋予失巢凋亡对误移细胞的抵抗力，从而促进其他组织的侵袭。这种BMP门控的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。集体细胞迁移过程中的质量控制对于正确的器官组装至关重要。Macabenta等表明果蝇胚胎肌肉前体利用分泌的BMP配体来协调有丝分裂沿着细胞死亡基因Hid的表达，其消除了在迁移期间失去与基质衍生的FGF配体的通路的细胞。
Tissue homeostasis involves the elimination of abnormal cells to avoid compromised patterning and function. While 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 cell death gene head involution defective is responsible for caudal visceral mesoderm (CVM) anoikis. 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, facilitating invasion of other tissues. This BMP-gated cell cycle checkpoint defines a quality control mechanism during mesenchymal collective migration. Quality control during collective cell migration is essential for proper organ assembly. Macabenta et al. show that Drosophila embryonic muscle precursors utilize secreted BMP ligand to coordinate mitosis along with concomitant expression of the cell death gene Hid, which eliminates cells that lose access to substrate-derived FGF ligand during migration.
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