Hassan, O. A. | bioRxiv Science

bioRxiv2024

Apical Size Reduction by Macropinocytosis Alleviates Tissue Crowding

Tissue crowding represents a critical challenge to epithelial tissues, which often respond via the irreversible process of live cell extrusion. We report cell size reduction via macropinocytosis as an alternative mechanism. Macropinocytosis is triggered by tissue crowding via mechanosensory signaling, leading to substantial internalization of apical membrane and driving a reduction in apical cell size that remodels the epithelium to alleviate crowding. We report that this mechanism regulates the long-term organization of developing epithelium in response to proliferation-induced crowding but also serves as an immediate response to acute external compression. In both cases, inhibiting macropinocytosis induces a dramatic increase in cell extrusion suggesting cooperation between cell extrusion and macropinocytosis in response to compression. Our findings implicate macropinocytosis as an important regulator of dynamic epithelial remodeling.

cell biology↗

bioRxiv2023

Bidirectional multiciliated cell extrusion is controlled by Notch driven basal extrusion and Piezo 1 driven apical extrusion.

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, receptivity 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 Piezo 1 such that premature activation of Piezo 1 leads to early extrusion while blocking Piezo 1 leads to MCC maintenance. Distinct mechansms for MCC loss underlie the importance of their removal during epithelial remodeling. Summay StatementCell extrusion typically occurs unidirectionally. We have identified a single population of multiciliated cells that extrudes bidirectionally: Notch-driven basal extrusion and Piezo 1-mediated apical extrusion.

cell biology↗