Precise alternating cellular pattern in the inner ear by coordinated hopping intercalations and delaminations

The mammalian hearing organ, the organ of Corti, is one of the most organized tissues in the mammalian body plan. It contains precisely positioned array of alternating sensory hair cells (HC) and non-sensory supporting cells that emerge during embryonic development from an initially disordered pro-sensory domain. While much is known about the genetic elements involved in this process, it is still unclear how such precise alternating patterns emerge during embryonic development. Here, we combine live imaging of mouse inner ear explants with hybrid mechano-regulatory models to elucidate the mechanisms underlying the formation of a single row of inner HC (IHC). We identify three processes that contribute to the formation of a single IHC row. First, we identify a new morphological transition, termed ‘hopping intercalation’, that allows differentiating Atoh1+ cells to physically ‘hop’ under the apical plane into their final position. Second, we show that Atoh1+ cells that express low levels of Atoh1 delaminate. Finally, we use laser ablation to show that differential adhesion between different cell types contributes to straightening of the IHC row. Our experimental results and modeling thus support a mechanism for precise patterning based on coordination between signaling mediated differentiation and mechanically driven organization that is likely relevant for many developmental processes.