Mechanochemical symmetry breaking during morphogenesis of lateral-line sensory organs


Actively regulated symmetry breaking, which is ubiquitous in biological cells, underlies phenomena such as directed cellular movement and morphological polarization. Here, we investigate how an organ-level polarity pattern emerges through symmetry breaking at the cellular level during the formation of a mechanosensory organ. Combining theory, genetic perturbations and in vivo imaging, we study the development and regeneration of the fluid-motion sensors in the zebrafish’s lateral line. We find that two interacting symmetry-breaking events—one mediated by biochemical signalling and the other by cellular mechanics—give rise to precise rotations of cell pairs, which produce a mirror-symmetric polarity pattern in the receptor organ.

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Fig. 1: Mirror-symmetric polarity pattern in lateral-line neuromasts.
Fig. 2: Contact-angle dynamics of maturing hair-cell pairs.
Fig. 3: Relationship of polarity to cellular movements.
Fig. 4: Surface mechanics of hair-cell maturation and active dipole transitions.
Fig. 5: Relation of hair-cell doublet shapes to surface-tension gradients.
Fig. 6: Symmetry-breaking events underlying polarity patterning.

Data availability

Source data are available for this paper. All other data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.


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We thank A. Kaczynska for expert fish husbandry and A. Mietke, E. Siggia and the members of our research group for critical reading and comments on the manuscript. A.E. was supported by a Feodor Lynen Fellowship from the Alexander von Humboldt Foundation and A.J. by an F.M. Kirby Postdoctoral Fellowship from Rockefeller University. A.D. is a Postdoctoral Associate and A.J.H. an Investigator of Howard Hughes Medical Institute.

Author information




A.E. and A.J. designed the research with contributions from A.D. and A.J.H. A.J. performed the experiments with contributions from A.D. A.E. developed the theory. A.E. and A.J. analysed the data. A.E. wrote the paper with contributions from A.J., A.D. and A.J.H.

Corresponding authors

Correspondence to A. Erzberger or A. J. Hudspeth.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–9, Videos 1–4, note and references.

Reporting Summary

Supplementary Video 1

Sensory hair cells in a lateral line neuromast. In a confocal recording enhanced by content-aware image restoration (CARE), a scan from the apex to the base of a neuromast in a four-day-old Tg(myo6b:actb1-EGFP) zebrafish larva shows sensory hair cells labeled with β-actin–GFP. The orientation of each hair bundle is revealed by the location of the kinocilium, which appears as a dark spot on the actin-enriched apical surface of each hair cell.

Supplementary Video 2

Deep-learning-assisted, long-term imaging of hair-cell maturation. A maximum-intensity projection of a time-lapse recording shows a developing neuromast in a Tg(myo6b:actb1-EGFP) zebrafish larva. We used content-aware image restoration (CARE; right) to improve the signal-to-noise ratio in images taken at low laser power and short exposure times (left). Minimizing photo-induced damage to the sample allowed us to image cell pairs throughout their maturation at high spatiotemporal resolution. Note the appearance of a new pair of hair cells in the lower left, followed by a second pair in the upper region. Each pair of daughter cells is initially rounded, with a flat contact surface between the cells. During a subsequent phase of protrusive activity the cells separate from one another. Finally, distinct apical surfaces with oppositely polarized hair bundles appear. In this and Supplementary Video 3 and 4, the time signal is in hours and minutes.

Supplementary Video 3

Hair-cell maturation in a Notch mutant larva. A CARE-processed maximum-intensity projection of a time-lapse recording depicts a developing neuromast in a Tg(myo6b:actb1-EGFP) animal lacking functional Notch1a receptors (Notch1ab638/b638 mutant). The sensory hair-cell pairs form uniformly oriented actin protrusions during maturation and develop uniformly oriented hair bundles. Note the young pair of hair cells at the lower edge of the neuromast, both of which develop hair bundles oriented toward the animal’s posterior. A second pair of nascent hair cells appears after four hours at the neuromast’s upper margin.

Supplementary Video 4

Dipole transition of a pair of nascent hair cells. A CARE-enhanced time-lapse recording of a developing neuromast in a Tg(myo6b:actb1-EGFP) zebrafish larva is focussed at the level of hair cell-nuclei. The arrowhead in the first image denotes the location at which a progenitor cell appears and undergoes a division, giving rise to a pair of nascent hair cells. The two daughter cells maintain a flattened contact surface and undergo a rearrangement in which they switch positions along the PCP axis between 6:50 and 8:50. A second division near the upper edge of the neuromast yields a pair of cells that do not exchange places.

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Erzberger, A., Jacobo, A., Dasgupta, A. et al. Mechanochemical symmetry breaking during morphogenesis of lateral-line sensory organs. Nat. Phys. 16, 949–957 (2020).

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