The Clustered Gamma Protocadherin Pcdhγc4 Isoform Regulates Cortical Interneuron Programmed Cell Death in the Mouse Cortex

Walter Mancia Leon; David Steffen; Fiona Dale-Huang; Benjamin Rakela; Arnar Breevoort; Ricardo Romero-Rodriguez; Andrea Hasenstaub; Michael Stryker; Joshua Weiner; Arturo Alvarez-Buylla

doi:10.1101/2023.02.03.526887

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The Clustered Gamma Protocadherin Pcdhγc4 Isoform Regulates Cortical Interneuron Programmed Cell Death in the Mouse Cortex

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The Clustered Gamma Protocadherin Pcdhγc4 Isoform Regulates Cortical Interneuron Programmed Cell Death in the Mouse Cortex

Walter Mancia Leon, David Steffen, Fiona Dale-Huang, Benjamin Rakela, Arnar Breevoort, Ricardo Romero-Rodriguez, Andrea Hasenstaub, Michael Stryker, Joshua Weiner and Arturo Alvarez-Buylla

bioRxiv

Cold Spring Harbor Laboratory Press

02/06/2023

DOI: 10.1101/2023.02.03.526887

PMCID: PMC9915683

PMID: 36778455

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https://doi.org/10.1101/2023.02.03.526887View

Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Cortical function critically depends on inhibitory/excitatory balance. Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers are adjusted by programmed cell death. Previously, we showed that loss of clustered gamma protocadherins (Pcdhγ), but not of genes in the alpha or beta clusters, increased dramatically cIN BAX-dependent cell death in mice. Here we show that the sole deletion of the Pcdhγc4 isoform, but not of the other 21 isoforms in the Pcdhγ gene cluster, increased cIN cell death in mice during the normal period of programmed cell death. Viral expression of the Pcdhγc4 isoform rescued transplanted cINs lacking Pcdhγ from cell death. We conclude that Pcdhγ, specifically Pcdhγc4, plays a critical role in regulating the survival of cINs during their normal period of cell death. This demonstrates a novel specificity in the role of Pcdhγ isoforms in cortical development. Competing Interest Statement Arturo Alvarez-Buylla is cofounder, serves on the scientific advisory board, and owns shares in Neurona Therapeutics. Footnotes * Updated authors Orcid ID

Apoptosis

Bax protein

Cell death

Cell migration

Forebrain

Interneurons

Isoforms

Protocadherin

Details

Title: Subtitle: The Clustered Gamma Protocadherin Pcdhγc4 Isoform Regulates Cortical Interneuron Programmed Cell Death in the Mouse Cortex
Creators: Walter Mancia Leon
David Steffen
Fiona Dale-Huang
Benjamin Rakela
Arnar Breevoort
Ricardo Romero-Rodriguez
Andrea Hasenstaub
Michael Stryker
Joshua Weiner
Arturo Alvarez-Buylla
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2023.02.03.526887
PMID: 36778455
PMCID: PMC9915683
Publisher: Cold Spring Harbor Laboratory Press; Cold Spring Harbor
Language: English
Date posted: 02/06/2023
Academic Unit: Liberal Arts and Science Admin; Psychiatry; Iowa Neuroscience Institute; Biology
Record Identifier: 9984365912302771

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