γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons

Meltzer, S.; Comeau, K.; Chirila, A.; Osei-Asante, E.; DeLisle, M.; Zhang, Q.; Kalish, B. T.; Tasnim, A.; Huey, E.; Fuller, L. C.; Flaherty, E. K.; Lefebvre, J. L.; Maniatis, T.; Garrett, A. M.; Weiner, J. A.; Ginty, D. D.

doi:10.1101/2022.05.25.493080

bioRxiv · 10.1101/2022.05.25.493080

γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons

Meltzer, S.·Comeau, K.·Chirila, A.·Osei-Asante, E.·DeLisle, M.·Zhang, Q.·Kalish, B. T.·Tasnim, A.·Huey, E.·Fuller, L. C.·Flaherty, E. K.·Lefebvre, J. L.·Maniatis, T.·Garrett, A. M.·Weiner, J. A.·Ginty, D. D.

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Abstract

Light touch sensation begins with activation of low-threshold mechanoreceptor (LTMR) endings in the skin and propagation of their signals to the spinal cord and brainstem. We found that the clustered protocadherin gamma (Pcdhg) gene locus, which encodes 22 cell-surface homophilic binding proteins, is required in somatosensory neurons for normal behavioral reactivity to a range of tactile stimuli. Developmentally, distinct Pcdhg isoforms mediate LTMR synapse formation through neuron-neuron interactions and peripheral axonal branching through neuron-glia interactions. The Pcdhgc3 isoform mediates homophilic interactions between sensory axons and spinal cord neurons to promote synapse formation in vivo, and is sufficient to induce postsynaptic specializations in vitro. Moreover, loss of Pcdhgs and somatosensory synaptic inputs to the dorsal horn lead to fewer corticospinal synapses onto dorsal horn neurons. These findings reveal essential roles for Pcdhg isoform diversity in somatosensory neuron synapse formation, peripheral axonal branching, and step-wise assembly of central mechanosensory circuitry.

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Meltzer, S., Comeau, K., Chirila, A., Osei-Asante, E., DeLisle, M., Zhang, Q., Kalish, B. T., Tasnim, A., Huey, E., Fuller, L. C., Flaherty, E. K., Lefebvre, J. L., Maniatis, T., Garrett, A. M., Weiner, J. A., Ginty, D. D.. 2022-05-25. γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons. https://doi.org/10.1101/2022.05.25.493080

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