Differential turnover of apicobasal regulators drives emergent mechano-response and shape homeostasis
Abstract
Epithelial cell shape plays a fundamental role in tissue dynamics. Numerous studies have established how cells drastically change their shape to promote epithelial tissue morphogenesis. However, the mechanisms enabling cells to maintain their shape remain far less understood. Here, leveraging live imaging in Drosophila epithelial tissue and theoretical modeling, we identify an emergent mechano-chemical feedback that ensures junction length and cell shape stability, without requiring a dedicated molecular force sensor. We find that an increase in junction length is associated with a passive dilution of E-Cadherin, followed by an increase in Myosin-II-dependent contractility that reduces junction length. Theoretically, we show that this regulation of junction length generically emerges when negative and positive regulators of contractility have distinct kinetics. Experiments confirm that E-Cadherin acts as a negative regulator with slow turnover. Mechanistically, local dilution of E-Cadherin passively lifts an inhibition on lateral apicobasal polarity components, allowing the RhoGEF Cyst — with its fast turnover — to accumulate and increase contractility. Perturbing this feedback results in aberrant cell junction and shape regulation, thereby compromising the ability of the tissue to buffer local mechanical fluctuations and global mechanical stresses. Altogether, we propose that differential turnover between apical and lateral polarity complexes provides an emergent mechano-response for junction length and cell shape homeostasis.
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BibTeX
@misc{lopezgay2026differential,
title = {{Differential turnover of apicobasal regulators drives emergent mechano-response and shape homeostasis}},
author = {Jesús López-Gay and Uday Ram Gubbala and Priscillia Pierre-Elies and Ines Cristo and Diana Pinheiro and Edouard Hannezo and Yohanns Bellaiche},
howpublished = {HAL},
year = {2026},
month = aug,
url = {https://hal.science/hal-05767902v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - Differential turnover of apicobasal regulators drives emergent mechano-response and shape homeostasis
AU - Jesús López-Gay
AU - Uday Ram Gubbala
AU - Priscillia Pierre-Elies
AU - Ines Cristo
AU - Diana Pinheiro
AU - Edouard Hannezo
AU - Yohanns Bellaiche
PY - 2026
DA - 2026/08/12
PB - HAL
UR - https://hal.science/hal-05767902v1
AB - Epithelial cell shape plays a fundamental role in tissue dynamics. Numerous studies have established how cells drastically change their shape to promote epithelial tissue morphogenesis. However, the mechanisms enabling cells to maintain their shape remain far less understood. Here, leveraging live imaging in Drosophila epithelial tissue and theoretical modeling, we identify an emergent mechano-chemical feedback that ensures junction length and cell shape stability, without requiring a dedicated molecular force sensor. We find that an increase in junction length is associated with a passive dilution of E-Cadherin, followed by an increase in Myosin-II-dependent contractility that reduces junction length. Theoretically, we show that this regulation of junction length generically emerges when negative and positive regulators of contractility have distinct kinetics. Experiments confirm that E-Cadherin acts as a negative regulator with slow turnover. Mechanistically, local dilution of E-Cadherin passively lifts an inhibition on lateral apicobasal polarity components, allowing the RhoGEF Cyst — with its fast turnover — to accumulate and increase contractility. Perturbing this feedback results in aberrant cell junction and shape regulation, thereby compromising the ability of the tissue to buffer local mechanical fluctuations and global mechanical stresses. Altogether, we propose that differential turnover between apical and lateral polarity complexes provides an emergent mechano-response for junction length and cell shape homeostasis.
ER -