Clustered gamma-protocadherins regulate cortical interneuron programmed cell death.

Walter R Mancia Leon, Julien Spatazza, Benjamin Rakela, Ankita Chatterjee, Viraj Pande, Tom Maniatis, Andrea R Hasenstaub, Michael P Stryker, Arturo Alvarez-Buylla

eLife 2020 Jul 07

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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. © 2020, Mancia Leon et al.

Citation

Walter R Mancia Leon, Julien Spatazza, Benjamin Rakela, Ankita Chatterjee, Viraj Pande, Tom Maniatis, Andrea R Hasenstaub, Michael P Stryker, Arturo Alvarez-Buylla. Clustered gamma-protocadherins regulate cortical interneuron programmed cell death. eLife. 2020 Jul 07;9