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

View ORCID ProfileShan Meltzer, Katelyn Comeau, Anda Chirila, Emmanuella Osei-Asante, Michelle DeLisle, Qiyu Zhang, Brian T. Kalish, Aniqa Tasnim, Erica Huey, Leah C. Fuller, Erin K. Flaherty, Julie L. Lefebvre, Tom Maniatis, View ORCID ProfileAndrew M. Garrett, Joshua A. Weiner, David D. Ginty
doi: https://doi.org/10.1101/2022.05.25.493080
Shan Meltzer
1Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
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  • ORCID record for Shan Meltzer
Katelyn Comeau
1Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
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Anda Chirila
1Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
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Emmanuella Osei-Asante
1Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
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Michelle DeLisle
1Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
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Qiyu Zhang
1Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
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Brian T. Kalish
2Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
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Aniqa Tasnim
1Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
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Erica Huey
1Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
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Leah C. Fuller
3Department of Biology and Iowa Neuroscience Institute, University of Iowa, 143 Biology Building, Iowa City, IA, 52242, USA
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Erin K. Flaherty
4Department of Biochemistry and Molecular Biophysics, Zuckerman Institute of Mind Brain and Behavior, Columbia University, New York, NY, 10032, USA
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Julie L. Lefebvre
5Department of Molecular Genetics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
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Tom Maniatis
4Department of Biochemistry and Molecular Biophysics, Zuckerman Institute of Mind Brain and Behavior, Columbia University, New York, NY, 10032, USA
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Andrew M. Garrett
6Department of Pharmacology and Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield St. 7322 Scott Hall, Detroit, MI 48201, USA
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Joshua A. Weiner
3Department of Biology and Iowa Neuroscience Institute, University of Iowa, 143 Biology Building, Iowa City, IA, 52242, USA
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David D. Ginty
1Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
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  • For correspondence: david_ginty@hms.harvard.edu
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Summary

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 Statement

The authors have declared no competing interest.

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Posted May 25, 2022.
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γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons
Shan Meltzer, Katelyn Comeau, Anda Chirila, Emmanuella Osei-Asante, Michelle DeLisle, Qiyu Zhang, Brian T. Kalish, Aniqa Tasnim, Erica Huey, Leah C. Fuller, Erin K. Flaherty, Julie L. Lefebvre, Tom Maniatis, Andrew M. Garrett, Joshua A. Weiner, David D. Ginty
bioRxiv 2022.05.25.493080; doi: https://doi.org/10.1101/2022.05.25.493080
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γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons
Shan Meltzer, Katelyn Comeau, Anda Chirila, Emmanuella Osei-Asante, Michelle DeLisle, Qiyu Zhang, Brian T. Kalish, Aniqa Tasnim, Erica Huey, Leah C. Fuller, Erin K. Flaherty, Julie L. Lefebvre, Tom Maniatis, Andrew M. Garrett, Joshua A. Weiner, David D. Ginty
bioRxiv 2022.05.25.493080; doi: https://doi.org/10.1101/2022.05.25.493080

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