# The Rho GTPase regulator ARHGEF3 orchestrates hair placode budding by coordinating cell fate and P-cadherin patterning in mice

## TL;DR

This study shows how ARHGEF3 helps organize cells during early hair follicle development in mice by controlling cadherin patterns and cell fate.

## Contribution

ARHGEF3 is identified as a novel regulator of cadherin patterning and placode polarization during hair follicle development.

## Key findings

- ARHGEF3 restricts cell fate acquisition and establishes a P-cadherin gradient in hair placodes.
- Arhgef3 knockout leads to enlarged placodes with disrupted P-cadherin gradients and abnormal hair follicle downgrowth.
- The study suggests ARHGEF3 has broader roles in epithelial appendage morphogenesis.

## Abstract

During embryogenesis, cells self-organize into precise patterns that enable tissues and organs to acquire specialized functions. Despite its importance, the molecular choreography driving these collective cellular behaviors remains poorly understood, posing a major challenge in developmental biology and limiting progress in regenerative medicine. Here, we use the developing mouse hair follicle as a model mini-organ to investigate the early events of epithelial bud formation. We identify the Rho GTPase regulator ARHGEF3 as a critical upstream factor that restricts cell fate acquisition and establishes a radial gradient of P-cadherin across the placode during early hair follicle development. In Arhgef3 knockout embryos, placodes are enlarged and exhibit elevated P-cadherin levels at cell-cell junctions, disrupting gradient formation without affecting E-cadherin distribution. This defect correlates with aberrant epithelial organization and increased incidence of straight hair follicle downgrowth. Our findings position ARHGEF3 as a novel regulator of cadherin patterning and placode polarization, and suggest broader roles in the morphogenesis of other epithelial appendages governed by similar developmental programs.

During embryogenesis, cells self-organize into patterns that support tissue-specific functions, but how these collective cellular behaviors are coordinated remains unclear. This study shows that the Rho GTPase regulator, ARHGEF3, regulates cadherin patterning and placode polarization in early hair follicle development, influencing epithelial organization and morphogenesis.