Errors in early embryogenesis are a cause of sporadic cell death and developmental failure^1,2. Phagocytic activity has a central role in scavenging apoptotic cells in differentiated tissues^3,4,5,6. However, how apoptotic cells are cleared in the blastula embryo in the absence of specialized immune cells remains unknown. Here we show that the surface epithelium of zebrafish and mouse embryos, which is the first tissue formed during vertebrate development, performs efficient phagocytic clearance of apoptotic cells through phosphatidylserine-mediated target recognition. Quantitative four-dimensional in vivo imaging analyses reveal a collective epithelial clearance mechanism that is based on mechanical cooperation by two types of Rac1-dependent basal epithelial protrusions. The first type of protrusion, phagocytic cups, mediates apoptotic target uptake. The second, a previously undescribed type of fast and extended actin-based protrusion that we call ‘epithelial arms’, promotes the rapid dispersal of apoptotic targets through Arp2/3-dependent mechanical pushing. On the basis of experimental data and modelling, we show that mechanical load-sharing enables the long-range cooperative uptake of apoptotic cells by multiple epithelial cells. This optimizes the efficiency of tissue clearance by extending the limited spatial exploration range and local uptake capacity of non-motile epithelial cells. Our findings show that epithelial tissue clearance facilitates error correction that is relevant to the developmental robustness and survival of the embryo, revealing the presence of an innate immune function in the earliest stages of embryonic development.

早期胚胎发生的错误是零星细胞死亡和发育失败的原因^1,2。吞噬活性在清除分化组织中的凋亡细胞方面起着核心作用^3,4,5,6. 然而，在没有专门的免疫细胞的情况下，囊胚胚胎中的凋亡细胞是如何被清除的仍然未知。在这里，我们展示了斑马鱼和小鼠胚胎的表面上皮，这是脊椎动物发育过程中形成的第一个组织，通过磷脂酰丝氨酸介导的目标识别对凋亡细胞进行有效的吞噬清除。定量四维体内成像分析揭示了一种集体上皮清除机制，该机制基于两种类型的 Rac1 依赖性基底上皮突起的机械合作。第一种突起，吞噬杯，介导凋亡靶标摄取。第二种，一种以前未描述的基于肌动蛋白的快速和扩展的突起类型，我们称之为“上皮臂”，通过依赖 Arp2/3 的机械推动促进凋亡靶标的快速分散。在实验数据和建模的基础上，我们表明机械负载共享可以使多个上皮细胞远程协同摄取凋亡细胞。这通过扩展非运动上皮细胞的有限空间探索范围和局部摄取能力来优化组织清除的效率。我们的研究结果表明，上皮组织清除促进了与胚胎发育稳健性和存活相关的错误纠正，揭示了胚胎发育早期阶段先天免疫功能的存在。我们表明，机械负载共享能够使多个上皮细胞远程协同摄取凋亡细胞。这通过扩展非运动上皮细胞的有限空间探索范围和局部摄取能力来优化组织清除的效率。我们的研究结果表明，上皮组织清除促进了与胚胎发育稳健性和存活相关的错误纠正，揭示了胚胎发育早期阶段先天免疫功能的存在。我们表明，机械负载共享能够使多个上皮细胞远程协同摄取凋亡细胞。这通过扩展非运动上皮细胞的有限空间探索范围和局部摄取能力来优化组织清除的效率。我们的研究结果表明，上皮组织清除促进了与胚胎发育稳健性和存活相关的错误纠正，揭示了胚胎发育早期阶段先天免疫功能的存在。