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Publication : Loss of Clustered Protocadherin Diversity Alters the Spatial Distribution of Cortical Interneurons in Mice.

First Author  Gallerani N Year  2020
Journal  Cereb Cortex Commun Volume  1
Issue  1 Pages  tgaa089
PubMed ID  34296145 Mgi Jnum  J:305581
Mgi Id  MGI:6711200 Doi  10.1093/texcom/tgaa089
Citation  Gallerani N, et al. (2020) Loss of Clustered Protocadherin Diversity Alters the Spatial Distribution of Cortical Interneurons in Mice. Cereb Cortex Commun 1(1):1-12
abstractText  Cortical interneurons (cINs) are locally projecting inhibitory neurons that are distributed throughout the cortex. Due to their relatively limited range of influence, their arrangement in the cortex is critical to their function. cINs achieve this arrangement through a process of tangential and radial migration and apoptosis during development. In this study, we investigated the role of clustered protocadherins (cPcdhs) in establishing the spatial patterning of cINs through the use of genetic cPcdh knockout mice. cPcdhs are expressed in cINs and are known to play key functions in cell spacing and cell survival, but their role in cINs is poorly understood. Using spatial statistical analysis, we found that the 2 main subclasses of cINs, parvalbumin-expressing and somatostatin-expressing (SST) cINs, are nonrandomly spaced within subclass but randomly with respect to each other. We also found that the relative laminar distribution of each subclass was distinctly altered in whole α- or β-cluster mutants. Examination of perinatal time points revealed that the mutant phenotypes emerged relatively late, suggesting that cPcdhs may be acting during cIN morphological elaboration and synaptogenesis. We then analyzed an isoform-specific knockout for pcdh-αc2 and found that it recapitulated the α-cluster knockout but only in SST cells, suggesting that subtype-specific expression of cPcdh isoforms may help govern subtype-specific spatial distribution.
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