PT  - JOURNAL ARTICLE
AU  - Shan Meltzer
AU  - Katelyn Comeau
AU  - Anda Chirila
AU  - Emmanuella Osei-Asante
AU  - Michelle DeLisle
AU  - Qiyu Zhang
AU  - Brian T. Kalish
AU  - Aniqa Tasnim
AU  - Erica Huey
AU  - Leah C. Fuller
AU  - Erin K. Flaherty
AU  - Julie L. Lefebvre
AU  - Tom Maniatis
AU  - Andrew M. Garrett
AU  - Joshua A. Weiner
AU  - David D. Ginty
TI  - γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons
AID  - 10.1101/2022.05.25.493080
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.25.493080
4099  - http://biorxiv.org/content/early/2022/05/25/2022.05.25.493080.short
4100  - http://biorxiv.org/content/early/2022/05/25/2022.05.25.493080.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.