Hair cell identity establishes labeled lines of directional mechanosensation

Abstract

Directional mechanoreception by hair cells is transmitted to the brain via afferent neurons to enable postural control and rheotaxis. Neuronal tuning to individual directions of mechanical flow occurs when each peripheral axon selectively synapses with multiple hair cells of identical planar polarization. How such mechanosensory labeled lines are established and maintained remains unsolved. Here, we use the zebrafish lateral line to reveal that asymmetric activity of the transcription factor Emx2 diversifies hair cell identity to instruct polarity-selective synaptogenesis. Unexpectedly, presynaptic scaffolds and coherent hair cell orientation are dispensable for synaptic selectivity, indicating that epithelial planar polarity and synaptic partner matching are separable. Moreover, regenerating axons recapitulate synapses with hair cells according to Emx2 expression but not global orientation. Our results identify a simple cellular algorithm that solves the selectivity task even in the presence of noise generated by the frequent receptor cell turnover. They also suggest that coupling connectivity patterns to cellular identity rather than polarity relaxes developmental and evolutionary constraints to innervation of organs with differing orientation.

A neuronal blueprint for directional mechanosensation in larval zebrafish

“…To test lateral-line somatotopy functionally, we used a combination of pLAN map rewiring and a rheotaxis assay. In previous studies, we found that after peripheral nerve transection LANs regenerate axons to re-innervate neuromasts within 36 h 18,44 . Regenerating axons reproduce synapses with hair cells of the original planar polarization, recapitulating neuronal directional tuning 18,44 .…”

“…In previous studies, we found that after peripheral nerve transection LANs regenerate axons to re-innervate neuromasts within 36 h 18,44 . Regenerating axons reproduce synapses with hair cells of the original planar polarization, recapitulating neuronal directional tuning 18,44 . However, they nearly always re-innervate a neuromast different from the original with a strong bias toward more caudal neuromasts, which strongly disrupts lateralis somatotopy 18 .…”

“…Individually marked LANs were traced from the periphery to the brain by light microscopy 13,19 ( Figure 1B). Because LANs present a conspicuous arborization below neuromasts and stereotypic connectivity with hair cells, we could unambiguously assign both the spatial receptivity (localization of the innervated neuromast) and the directional tuning of each neuron (Figure S1C) 18 . The resulting raw images were stitched together and skeletonized ( Figures 1C and 1D).…”

“…LANs central projections form a central lintel (LCL) with laminar organization, which coarsely represents the spatial distribution of neuromasts via a topographic (somatotopic) arrangement ( Figures 1A and 1B) 10,12,17 . Each neuromast is normally innervated by 4 LANs 13,15,18 . As each LAN selectively synapses with multiple hair cells of identical orientation (Figures S1A and S1C), neurons are effectively tuned to a single direction of mechanical stimuli [18][19][20] .…”

“…Each neuromast is normally innervated by 4 LANs 13,15,18 . As each LAN selectively synapses with multiple hair cells of identical orientation (Figures S1A and S1C), neurons are effectively tuned to a single direction of mechanical stimuli [18][19][20] . LANs have a small receptive field restricted to the immediacy of the innervated neuromast, sampling ipsilateral local hydrodynamics 21 .…”