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

KOZAK, EVA L.; MIRANDA-RODRÍGUEZ, JERÓNIMO R.; BORGES, AUGUSTO; DIERKES, KAI; MINEO, ALESSANDRO; PINTO-TEIXEIRA, FILIPE; VIADER-LLARGUÉS, ORIOL; SOLON, JÉRÔME; CHARA, OSVALDO; LÓPEZ-SCHIER, HERNÁN

DEVELOPMENT

COMPANY OF BIOLOGISTS LTD

Año: 2023 vol. 150

0950-1991

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° around their geometric center after acquiring different identities via Notch1amediated 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.