# Actomyosin contractility and a threshold of cadherin cell adhesion are required during tissue fusion

## TL;DR

This study reveals how actomyosin contractility and cadherin adhesion drive tissue fusion in mammalian lip development and how their disruption can cause cleft lip.

## Contribution

The paper identifies a threshold requirement for cadherin adhesion and the role of p120-catenin in tissue fusion during development.

## Key findings

- Actomyosin contractility is essential for lip fusion, and its inhibition causes cleft lip.
- p120-catenin stabilizes cadherins but its RhoA and Kaiso binding is not required during development.
- Reduced cadherin levels disrupt the adhesion threshold needed for upper lip fusion.

## Abstract

Teng et al. investigate the cellular basis for tissue fusion during mammalian lip formation. They demonstrate that actomyosin contractility drives fusion, creating a threshold requirement for cadherin-based cell adhesion. These results also define p120-catenin molecular functions during development and implicate this mechanism in cleft lip, a common structural anomaly.

Tissue fusion is integral to mammalian morphogenesis, and its failure is a significant cause of structural anomalies, yet the underlying cellular mechanisms are incompletely understood. We examine cellular drivers of upper lip fusion in the mammalian embryo by establishing a live-imaging modality, revealing specific enrichment of F-actin that propagates in multicellular cables anchored at the fusion site. Actomyosin contractility drives lip fusion, and its pharmacological or genetic attenuation results in failed fusion and cleft lip. Generating a series of mice deficient in specific p120-catenin molecular functions, we reveal that p120-catenin binding to RhoA and Kaiso is dispensable during mammalian development, while stabilization of cadherins is crucial. Through generating an allelic series of new compound P-cadherin/E-cadherin mouse mutations disrupting combined cadherin levels, we unveil an elevated cadherin cell adhesion threshold requirement specific to upper lip fusion. Finally, we identify CDH3 variants in individuals with cleft lip, supporting the relevance of this mechanism in human tissue fusion.