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 mammals. It contains a precisely positioned array of alternating sensory hair cells (HCs) and nonsensory supporting cells. How such precise alternating patterns emerge during embryonic development is not well understood. Here, we combine live imaging of mouse inner ear explants with hybrid mechano-regulatory models to identify the processes that underlie the formation of a single row of inner hair cells (IHCs). First, we identify a previously unobserved morphological transition, termed "hopping intercalation,"that allows cells differentiating toward IHC fate to "hop"under the apical plane into their final position. Second, we show that out-of-row cells with low levels of the HC marker Atoh1 delaminate. Last, we show that differential adhesion between cell types contributes to straightening of the IHC row. Our results support a mechanism for precise patterning based on coordination between signaling and mechanical forces that is likely relevant for many developmental processes.