Department of Clinical Neurobiology, University Hospital and German Cancer Research Center, DKFZ, Heidelberg, 69120 Heidelberg, Germany.
Proc Natl Acad Sci U S A. 2012 Dec 4;109(49):20107-12. doi: 10.1073/pnas.1217103109. Epub 2012 Nov 19.
Connexins have been implicated in the regulation of precursor cell migration and proliferation during embryonic development of the mammalian brain. However, their function in postnatal neurogenesis is unclear. Here we demonstrate that connexin (Cx) 45 is expressed in transit-amplifying cells and neuroblasts in the postnatal subventricular zone (SVZ) and modulated the proliferation of SVZ-derived precursor cells in vivo. Thus, overexpression of Cx45 by retroviral injections increased the proliferation of Mash-1-positive transit-amplifying precursor cells in the SVZ. Conversely, conditional deletion of Cx45 in precursor cells decreased proliferation. Finally, we established that Cx45 positively influences cell cycle reentry via ATP signaling that involves intracellular calcium stores and ERK1/2 signaling.
间隙连接蛋白在哺乳动物大脑胚胎发育过程中对前体细胞的迁移和增殖起调节作用。然而,其在出生后神经发生中的功能尚不清楚。本研究表明,连接蛋白(Cx)45 在出生后侧脑室下区(SVZ)的过渡扩增细胞和神经母细胞中表达,并在体内调节 SVZ 来源的前体细胞的增殖。因此,通过逆转录病毒注射过表达 Cx45 可增加 SVZ 中 Mash-1 阳性过渡扩增前体细胞的增殖。相反,前体细胞中 Cx45 的条件性缺失会降低增殖。最后,我们确定 Cx45 通过涉及细胞内钙库和 ERK1/2 信号通路的 ATP 信号正向影响细胞周期再进入。