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.

Mechanical forces drive ordered patterning of hair cells in the mammalian inner ear.

Periodic organization of cells is required for the function of many organs and tissues. The development of such periodic patterns is typically associated with mechanisms based on intercellular signaling such as lateral inhibition and Turing patterning. Here we show that the transition from disordered to ordered checkerboard-like pattern of hair cells and supporting cells in the mammalian hearing organ, the organ of Corti, is likely based on mechanical forces rather than signaling events. Using time-lapse imaging of mouse cochlear explants, we show that hair cells rearrange gradually into a checkerboard-like pattern through a tissue-wide shear motion that coordinates intercalation and delamination events. Using mechanical models of the tissue, we show that global shear and local repulsion forces on hair cells are sufficient to drive the transition from disordered to ordered cellular pattern. Our findings suggest that mechanical forces drive ordered hair cell patterning in a process strikingly analogous to the process of shear-induced crystallization in polymer and granular physics.