Xenopus胚胎覆盖着一个复杂的上皮，其中包含大量的多纤毛细胞（MCCs）。在晚期发育阶段，上皮发生了剧烈的重组，导致MCCs完全消失。细胞推出是一种推动细胞损失但同时保持上皮屏障功能的过程。正常的细胞推出通常是单向的，而双向推出常常与疾病（例如癌症）相关。我们描述了两种不同的MCC推出机制，一种是由Notch信号驱动的基底推出，另一种是由Piezo1驱动的顶部推出。在该过程的早期，基底推出具有很强的偏向性，但随着发育的进行，向顶部推出的趋势逐渐增强。重要的是，对Notch信号的反应与年龄有关，由MCC转录程序的维持所调控，从而推迟该程序对细胞损失的保护作用。相比之下，后期顶部推出受Piezo1调控，过早激活Piezo1导致早期推出，而阻断Piezo1则维持了MCC的稳定。不同的MCC损失机制揭示了它们在上皮重组过程中被去除的重要性。©2023. The Company of Biologists有限公司出版。

Xenopus embryos are covered with a complex epithelium containing numerous multiciliated cells (MCCs). During late-stage development there is a dramatic remodeling of the epithelium that involves the complete loss of MCCs. Cell extrusion is a well-characterized process for driving cell loss while maintaining epithelial barrier function. Normal cell extrusion is typically unidirectional whereas bidirectional extrusion is often associated with disease (e.g. cancer). We describe two distinct mechanisms for MCC extrusion, a basal extrusion driven by Notch signaling and an apical extrusion driven by Piezo1. Early in the process there is a strong bias towards basal extrusion, but as development continues there is a shift towards apical extrusion. Importantly, response to the Notch signal is age-dependent and governed by the maintenance of the MCC transcriptional program such that extension of this program is protective against cell loss. In contrast, later apical extrusion is regulated by Piezo1 such that premature activation of Piezo1 leads to early extrusion while blocking Piezo1 leads to MCC maintenance. Distinct mechanisms for MCC loss underlie the importance of their removal during epithelial remodeling.© 2023. Published by The Company of Biologists Ltd.