Boundary-contact repolarization provides a mechanism for directional guidance of neural crest cell collectives

Abstract

Neural crest cells (NCCs) provide a well-established system for investigating collective migration during embryonic development and exhibit migratory behaviors with parallels to cancer invasion. Previous studies establish roles for co-attraction, contact inhibition of locomotion, polarity persistence, and tissue confinement in guiding NCC migration. However, it remains unclear whether NCC migration in confined environments occurs through spatial restriction alone or also through a repolarization response induced by contact with boundaries of confinement. By developing a computational model that couples self-generated chemical transport with contact-mediated repolarization and mechanical interactions, we show that cell-boundary contact can reorient cell polarity and sustain directional migration under confinement, whereas no persistent collective direction emerges without confinement. Moreover, suppressing contact-mediated repolarization from non-permissive confinement boundaries while preserving the mechanical interactions prevents sustained directional migration, suggesting that spatial restriction alone is insufficient in the model. Together, these findings establish an experimentally testable mechanism through which self-generated chemical signals and contact with confining tissues jointly regulate collective guidance of NCCs. These insights provide a basis for investigating developmental migration defects and potential strategies to regulate collective tissue invasion.