Atanasoski Suzana, Scherer Steven S, Sirkowski Erich, Leone Dino, Garratt Alistair N, Birchmeier Carmen, Suter Ueli
Institute of Cell Biology, Department of Biology, ETH Zurich, CH-8093 Zurich, Switzerland.
J Neurosci. 2006 Feb 15;26(7):2124-31. doi: 10.1523/JNEUROSCI.4594-05.2006.
Neuregulin/erbB signaling is critically required for survival and proliferation of Schwann cells as well as for establishing correct myelin thickness of peripheral nerves during development. In this study, we investigated whether erbB2 signaling in Schwann cells is also essential for the maintenance of myelinated peripheral nerves and for Schwann cell proliferation and survival after nerve injury. To this end, we used inducible Cre-loxP technology using a PLP-CreERT2 allele to ablate erbB2 in adult Schwann cells. ErbB2 expression was markedly reduced after induction of erbB2 gene disruption with no apparent effect on the maintenance of already established myelinated peripheral nerves. In contrast to development, Schwann cell proliferation and survival were not impaired in mutant animals after nerve injury, despite reduced levels of MAPK-P (phosphorylated mitogen-activated protein kinase) and cyclin D1. ErbB1 and erbB4 do not compensate for the loss of erbB2. We conclude that adult Schwann cells do not require major neuregulin signaling through erbB2 for proliferation and survival after nerve injury, in contrast to development and in cell culture.
在发育过程中,神经调节蛋白/erbB信号对于施万细胞的存活和增殖以及建立外周神经正确的髓鞘厚度至关重要。在本研究中,我们调查了施万细胞中的erbB2信号对于有髓外周神经的维持以及神经损伤后施万细胞的增殖和存活是否也必不可少。为此,我们使用诱导性Cre-loxP技术,利用PLP-CreERT2等位基因在成年施万细胞中敲除erbB2。在用erbB2基因破坏诱导后,erbB2表达明显降低,对已建立的有髓外周神经的维持没有明显影响。与发育过程不同,尽管丝裂原活化蛋白激酶磷酸化(MAPK-P)和细胞周期蛋白D1水平降低,但神经损伤后突变动物中的施万细胞增殖和存活并未受损。ErbB1和erbB4不能补偿erbB2的缺失。我们得出结论,与发育过程和细胞培养相反,成年施万细胞在神经损伤后的增殖和存活不需要通过erbB2的主要神经调节蛋白信号。