Gallerani Nicholas, Au Edmund
Department of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Department of Rehabilitative Medicine and Regeneration, Columbia University Irving Medical Center, New York, NY 10032, USA.
Cereb Cortex Commun. 2020 Nov 25;1(1):tgaa089. doi: 10.1093/texcom/tgaa089. eCollection 2020.
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.
皮层中间神经元（cINs）是局部投射的抑制性神经元，分布于整个皮层。由于其影响范围相对有限，它们在皮层中的排列对其功能至关重要。cINs在发育过程中通过切向和径向迁移以及凋亡过程实现这种排列。在本研究中，我们通过使用基因cPcdh敲除小鼠，研究了成簇原钙黏蛋白（cPcdhs）在建立cINs空间模式中的作用。cPcdhs在cINs中表达，已知在细胞间距和细胞存活中发挥关键作用，但其在cINs中的作用尚不清楚。通过空间统计分析，我们发现cINs的两个主要亚类，即表达小白蛋白的和表达生长抑素（SST）的cINs，在亚类内是非随机分布的，但彼此之间是随机分布的。我们还发现，在整个α或β簇突变体中，每个亚类的相对层状分布明显改变。对围产期时间点的检查显示，突变表型出现相对较晚，这表明cPcdhs可能在cIN形态细化和突触形成过程中起作用。然后我们分析了pcdh-αc2的亚型特异性敲除，发现它重现了α簇敲除，但仅在SST细胞中，这表明cPcdh亚型的亚型特异性表达可能有助于控制亚型特异性空间分布。
