Migrating neurons adapt motility modes to brain microenvironments via a mechanosensor, PIEZO1

Migration of newborn neurons is essential for brain morphogenesis and circuit formation, yet controversy exists regarding how neurons generate the driving force against strong mechanical stresses in crowded neural tissues. We found that cerebellar granule neurons adopt differential motility modes in distinct extracellular environments. In 3-dimensional (3D) confinement, actomyosin produces contractile forces at the posterior cell membrane, in addition to the traction force in the leading process that is exclusively observed in 2D cultures. The 3D migration is initiated by activation of a mechanosensitive channel PIEZO1. PIEZO1-induced calcium influx in the soma triggers the PKC-ezrin cascade, which recruits actomyosin to the posterior plasma membrane. Thus, migrating neurons use a mechano-sensing mechanism to activate multiple driving forces to maneuver in irregular brain tissue. One-Sentence SummaryCerebellar granule neurons use a mechanosensor PIEZO1 to switch migratory modes in confined spaces.