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

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 so-matosensory 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 post -synaptic specializations in vitro. Moreover, loss of Pcdhgs and somatosensory synaptic inputs to the dorsal horn leads to fewer corticospinal synapses on 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.

Automated summary

Light touch sensation begins with the activation of low-threshold mechanoreceptor (LTMR) endings and the transmission of their signals in the spinal cord and brainstem. The Pcdhg gene locus, encoding 22 cell-surface homophilic binding proteins, is crucial for normal behavioral reactivity to tactile stimuli in somatosensory neurons. Developmentally, different Pcdhg isoforms play roles in synapse formation and axonal branching of LTMR through neuron-neuron and neuron-glia interactions. Disruption of Pcdhg isoforms leads to fewer corticospinal synapses in the dorsal horn, highlighting their importance in the assembly of central mechanosensory circuitry.