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

Shan Meltzer; Katelyn C. Boulanger; Anda M. Chirila; Emmanuella Osei-Asante; Michelle DeLisle; Qiyu Zhang; Brian T. Kalish; Aniqa Tasnim; Erica L. Huey; Leah C. Fuller; Erin K. Flaherty; Tom Maniatis; Andrew M. Garrett; Joshua A. Weiner; David D. Ginty

doi:10.1016/j.neuron.2023.03.012

Back

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

Journal article

Open access

Peer reviewed

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

Shan Meltzer, Katelyn C. Boulanger, Anda M. Chirila, Emmanuella Osei-Asante, Michelle DeLisle, Qiyu Zhang, Brian T. Kalish, Aniqa Tasnim, Erica L. Huey, Leah C. Fuller, …

Neuron (Cambridge, Mass.), Vol.111(11), pp.1776-1794.e10

06/07/2023

DOI: 10.1016/j.neuron.2023.03.012

PMCID: PMC10365546

PMID: 37028432

Files and links (1)

url

https://doi.org/10.1016/j.neuron.2023.03.012View

Published (Version of record) Open Access

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 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.

Life Sciences & Biomedicine

Neurosciences

Neurosciences & Neurology

Science & Technology

Details

Title: Subtitle: γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons
Creators: Shan Meltzer - Harvard Medical School
Katelyn C. Boulanger - Harvard Medical School
Anda M. Chirila - Harvard Medical School
Emmanuella Osei-Asante - Harvard Medical School
Michelle DeLisle - Harvard Medical School
Qiyu Zhang - Harvard Medical School
Brian T. Kalish - Harvard Medical School
Aniqa Tasnim - Harvard Medical School
Erica L. Huey - Harvard Medical School
Leah C. Fuller - University of Iowa
Erin K. Flaherty - Columbia University
Tom Maniatis - Columbia University
Andrew M. Garrett - Wayne State University
Joshua A. Weiner - University of Iowa
David D. Ginty - Harvard Medical School
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.111(11), pp.1776-1794.e10
DOI: 10.1016/j.neuron.2023.03.012
PMID: 37028432
PMCID: PMC10365546
NLM abbreviation: Neuron
ISSN: 0896-6273
eISSN: 1097-4199
Publisher: Elsevier
Number of pages: 30
Grant note: NSFGRFP fellowship; National Science Foundation (NSF); NSF - Office of the Director (OD) 1R01 AT011447-01; R35 5R35NS097344-05; R01 NS055272; R01 EY031690; R01 5R01MH108579 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Stuart H.Q. amp; Victoria Quan Fellowship Hanna Gray Fellowship
Language: English
Date published: 06/07/2023
Academic Unit: Liberal Arts and Science Admin; Psychiatry; Iowa Neuroscience Institute; Biology
Record Identifier: 9984445528102771

Metrics

9 Record Views

22 Times Cited - Web of Science

See more details