Precise patterning in the inner ear
Abstract:
Precise periodic organization of cells is required for the function of many organs and tissues. It is often unclear, however, how such precise patterns emerge during development. The mammalian hearing organ, the organ of Corti, consists of a remarkably organized pattern of four rows of hair cells (HC) interspersed by non-sensory supporting cells (SC). These four rows further split into three rows of outer HC and one row of inner HC separated by a single row of pillar cells. The checkerboard-like pattern of HC and SC emerges from a disordered epithelium over several days, yet the transition from a disordered to an ordered cellular pattern is not well understood. Using time-lapse imaging of mouse cochlear explants and mathematical modeling, we show how mechanical forces drive dynamic intercalation and delamination events enabling the transition from an initially disordered salt-and-pepper pattern to a precisely organized pattern of HC and SC. We first show that the organization of the three outer HC rows is driven by a tissue-wide shear motion that coordinates intercalation and delamination events to achieve precision patterning. We next show that the single row of inner HCs is refined from an initial 2-3 rows wide salt-and-pepper pattern through a combination of two main morphological transitions: (i) A novel type of an intercalation process, termed ‘hopping intercalation’, where future HC ‘hop’ from one apical position to another. This is performed by sending a sub-apical protrusion that opens a new apical surface next to the pillar cell row. (ii) Cells that are selected to become HC, but fail to contact the pillar cell row, are delaminated and remove from the tissue. Mathematical modeling that combines feedback between regulatory processes (i.e. Notch mediated lateral inhibition) and mechanical processes can capture the main experimental observations and generates testable predictions. Overall, our experimental and theoretical analysis suggests that a feedback between Notch mediated differentiation and mechanically driven morphological transitions underlies the development of precise periodic HC patterning in the inner ear.
Sprinzak lab: https://www.sprinzak.sites.tau.ac.il/
