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Roles of A-kinase Anchor Protein 12 in Astrocyte and Oligodendrocyte Precursor Cell in Postnatal Corpus Callosum
Stem Cell Reviews and Reports ( IF 4.5 ) Pub Date : 2021-01-25 , DOI: 10.1007/s12015-021-10118-w
Hajime Takase 1, 2 , Gen Hamanaka 1 , Ryo Ohtomo 1 , Ji Hyun Park 1 , Kelly K Chung 1 , Irwin H Gelman 3 , Kyu-Won Kim 4 , Josephine Lok 1, 5 , Eng H Lo 1 , Ken Arai 1, 6
Affiliation  

The formation of the corpus callosum in the postnatal period is crucial for normal neurological function, and clinical genetic studies have identified an association of 6q24-25 microdeletion in this process. However, the mechanisms underlying corpus callosum formation and its critical gene(s) are not fully understood or identified. In this study, we examined the roles of AKAP12 in postnatal corpus callosum formation by focusing on the development of glial cells, because AKAP12 is coded on 6q25.1 and has recently been shown to play roles in the regulations of glial function. In mice, the levels of AKAP12 expression was confirmed to be larger in the corpus callosum compared to the cortex, and AKAP12 levels decreased with age both in the corpus callosum and cortex regions. In addition, astrocytes expressed AKAP12 in the corpus callosum after birth, but oligodendrocyte precursor cells (OPCs), another major type of glial cell in the developing corpus callosum, did not. Furthermore, compared to wild types, Akap12 knockout mice showed smaller numbers of both astrocytes and OPCs, along with slower development of corpus callosum after birth. These findings suggest that AKAP12 signaling may be required for postnatal glial formation in the corpus callosum through cell- and non-cell autonomous mechanisms.

Graphical Abstract



中文翻译:

A-激酶锚定蛋白 12 在出生后胼胝体星形胶质细胞和少突胶质细胞前体细胞中的作用

出生后胼胝体的形成对于正常的神经功能至关重要,临床遗传学研究已经确定了这一过程中 6q24-25 微缺失的关联。然而,胼胝体形成的潜在机制及其关键基因尚未完全了解或确定。在这项研究中,我们通过关注神经胶质细胞的发育来检查 AKAP12 在出生后胼胝体形成中的作用,因为AKAP12在 6q25.1 上编码,最近显示在神经胶质功能的调节中发挥作用。在小鼠中,与皮质相比,AKAP12 表达水平在胼胝体中被证实更高,并且 AKAP12 水平在胼胝体和皮质区域都随着年龄的增长而降低。此外,星形胶质细胞在出生后的胼胝体中表达 AKAP12,但发育中的胼胝体中的另一种主要神经胶质细胞少突胶质前体细胞 (OPC) 则不表达。此外,与野生型相比,Akap12敲除小鼠显示星形胶质细胞和 OPC 数量较少,出生后胼胝体发育较慢。这些发现表明,出生后胼胝体神经胶质细胞的形成可能需要 AKAP12 信号通过细胞和非细胞自主机制。

图形概要

更新日期:2021-01-25
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