# Apical size reduction by macropinocytosis alleviates tissue crowding

## TL;DR

Epithelial cells use macropinocytosis to shrink their top surface and reduce crowding, avoiding cell loss and offering a new way tissues adapt under stress.

## Contribution

Apical size reduction via macropinocytosis is a novel, reversible mechanism for epithelial tissue remodeling under crowding stress.

## Key findings

- Macropinocytosis reduces apical surface area to alleviate tissue crowding.
- Inhibiting macropinocytosis increases cell extrusion, showing cooperation between the two processes.
- Macropinocytosis responds to both developmental and external compression.

## Abstract

Tissue crowding represents a critical challenge to epithelial tissues, which often respond via the irreversible process of live cell extrusion. We report that apical size reduction via macropinocytosis serves as a malleable and less destructive form of tissue remodeling that can alleviate the need for cell loss. We find that macropinocytosis is triggered by tissue crowding via mechanosensory signaling, leading to substantial internalization of apical membrane. This drives a reduction in apical surface which alleviates crowding. We report that this mechanism regulates the long-term organization of the developing epithelium and controls the timing of proliferation-induced cell extrusion. Additionally, we observe a wave of macropinocytosis in response to acute external compression. In both scenarios, inhibiting macropinocytosis induces a dramatic increase in cell extrusion suggesting cooperation between cell extrusion and macropinocytosis in response to both developmental and external compression. Our findings implicate macropinocytosis as an important regulator of dynamic epithelial remodeling.

This study reveals that epithelial cells can reduce their apical surface area via macropinocytosis to relieve tissue crowding, offering a reversible alternative to cell extrusion and highlighting a new mechanism of tissue remodeling under stress.