Clustered gamma-protocadherins regulate cortical interneuron programmed cell death
- University of California San Francisco, United States
- Columbia University, United States
- University of California, San Francisco, United States
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. Here we show that loss of clustered gamma protocadherins (Pcdhg), but not of genes in the alpha or beta clusters, increased dramatically cIN BAX-dependent cell death in mice. Surprisingly, electrophysiological and morphological properties of Pcdhg-deficient and wild-type cINs during the period of cIN cell death were indistinguishable. Co-transplantation of wild-type with Pcdhg-deficient interneuron precursors further reduced mutant cIN survival, but the proportion of mutant and wild-type cells undergoing cell death was not affected by their density. Transplantation also allowed us to test for the contribution of Pcdhg isoforms to the regulation of cIN cell death. We conclude that Pcdhg, specifically Pcdhgc3, Pcdhgc4, and Pcdhgc5, play a critical role in regulating cIN survival during the endogenous period of programmed cIN death.
Data availability
Data generated for this study are included in the manuscript and source data files have been provided for Figures 1 to 13.
Article and author information
Author details
Andrea R Hasenstaub
Arturo Alvarez-Buylla
Funding
National Institutes of Health (R01NS028478)
- Arturo Alvarez-Buylla
National Institutes of Health (EY02517)
- Arturo Alvarez-Buylla
National Institutes of Health (R01DC014101)
- Andrea R Hasenstaub
National Institutes of Health (R01EY025174)
- Michael P Stryker
National Institutes of Health (5F32EY029935)
- Benjamin Rakela
- Michael P Stryker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sonia Garel, Ecole Normale Superieure, France
Ethics
Animal experimentation: Data presented in this study were acquired following the University of California, San Francisco (UCSF) Institutional Animal Care Committee guidelines under the following protocols: AN178775-02C, AN180588, AN175872.
Version history
- Received: January 22, 2020
- Accepted: July 6, 2020
- Accepted Manuscript published: July 7, 2020 (version 1)
- Version of Record published: July 21, 2020 (version 2)
Copyright
© 2020, Mancia Leon et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Clustered gamma-protocadherins regulate cortical interneuron programmed cell death
eLife 9:e55374.
https://doi.org/10.7554/eLife.55374
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