Long range juxtacrine signalling through cadherin for collective cell orientation

Many life phenomena, such as development, morphogenesis, tissue remodelling, and wound healing, are often driven by orderly and directional migration of collective cells. However, when cells are randomly oriented or localized disorder exists in orderly oriented collective cells, cell migration cannot occur in an orderly manner although various motion modes such as global rotation and local swirling and/or various motion patterns such as radial pattern and chiral pattern often occur. Therefore, it is important to control cell orientation to ensure the orderly migration of collective cells. Here, we show that it is not force transmission, but juxtacrine signalling through cadherin that plays a critical role in the orientation of collective cells. Surprisingly, juxtacrine signalling for cell orientation reached cells on a plastic dish that were not directly subjected to mechanical stimulation, up to 7 mm away from the actuator. The present study suggests that even weak mechanical stimulation is transmitted in a long range without force transmission through juxtacrine signalling. The long range juxtacrine signalling might play an important role in various life phenomena. STATEMENT OF SIGNIFICANCE: Juxtacrine signalling is direct cell-cell contact-dependent signalling, which plays a crucial role in cell behaviors such as mechanosensing, mechanotransduction and collective cell behaviors, however, there is not enough understanding about juxtacrine signalling. The present study has demonstrated that juxtacrine signalling for collective cell orientation is transmitted over a long range through cadherin. To the best of our knowledge, this is the first report of long range juxtacrine signalling. This finding may lead to the elucidation of various life phenomena such as development, morphogenesis, tissue remodelling, and wound healing.