Quantitative videomicroscopy reveals latent control of cell-pair rotations in vivo

Collective cell rotations are widely used during animal organogenesis. Theoretical and in vitro studies have conceptualized rotating cells as identical rigid-point objects that stochastically break symmetry to move monotonously and perpetually within an inert environment. However, it is unclear whether this notion can be extrapolated to a natural context, where rotations are ephemeral and heterogeneous cellular cohorts interact with an active epithelium. In zebrafish neuromasts, nascent sibling hair cells invert positions by rotating <= 180 degrees around their geometric center after acquiring different identities via Notch1a-mediated asymmetric repression of Emx2. Here, we show that this multicellular rotation is a three-phasic movement that progresses via coherent homotypic coupling and heterotypic junction remodeling. We found no correlation between rotations and epithelium-wide cellular flow or anisotropic resistive forces. Moreover, the Notch/Emx2 status of the cell dyad does not determine asymmetric interactions with the surrounding epithelium. Aided by computer modeling, we suggest that initial stochastic inhomogeneities generate a metastable state that poises cells to move and spontaneous intercellular coordination of the resulting instabilities enables persistently directional rotations, whereas Notch1a-determined symmetry breaking buffers rotational noise.

Automated summary

Collective cell rotations play an important role in animal organogenesis. This study investigates the multicellular rotation process in zebrafish neuromasts and reveals that it is a three-phasic movement involving homotypic coupling and junction remodeling. The rotations are not influenced by cellular flow or resistive forces and are unaffected by the Notch/Emx2 status of the cells. The findings suggest that initial stochastic inhomogeneities and intercellular coordination contribute to persistently directional rotations.