Disturbed apoptosis and cell proliferation in developing neuroepithelium of lumbo-sacral neural tubes in retinoic acid-induced spina bifida aperta in rat
Disturbed apoptosis and cell proliferation in developing neuroepithelium of lumbo-sacral neural tubes in retinoic acid-induced spina bifida aperta in rat
复制标题
视黄酸诱导的大鼠脊柱裂中腰骶神经管发育中神经上皮细胞凋亡和细胞增殖受到干扰
DOI：
10.1016/j.ijdevneu.2012.03.340
复制
发表时间：
2012-08-01
影响因子：
1.8
通讯作者：
Yuan, Zhengwei
中科院分区：
文献类型：
--
作者：
Wei, Xiaowei;Li, Hui;Yuan, Zhengwei
脊柱裂是一种复杂的先天性畸形，由胚胎发育过程中脊髓神经管融合失败引起。然而，脊柱裂的细胞机制还不完全清楚。在此，我们研究了全反式维甲酸(AtRA)诱导的胎鼠脊柱裂神经形成过程中全胚胎细胞凋亡和脊髓神经管内神经前体细胞的增殖情况。采用原位末端标记法对大鼠脊柱裂胚胎整体标本和连续切片标本进行细胞凋亡检测。通过有丝分裂标志物Ki67和PH3的染色来检测腰骶神经前体细胞的增殖情况。我们发现脊柱裂胚胎的神经上皮细胞存在过度的细胞凋亡，随着胚胎从E11到E13的发育，这种情况变得更加明显。相反，脊柱裂胚胎细胞增殖减少，与对照组相比差异逐渐增大，从E11到13。因此，atRA诱导的大鼠脊柱裂在胚胎发育过程中表现出神经前体细胞的凋亡和增殖受扰，这可能参与了脊柱裂的发病机制。(C)2012年综合业务数字网。爱思唯尔有限公司出版。保留所有权利。
Spina bifida is a complex congenital malformation resulting from failure of fusion in the spinal neural tube during embryogenesis. However, the cellular mechanism underlying spina bifida is not fully understood. Here, we investigated cell apoptosis in whole embryos and proliferation of neural progenitor cells in the spinal neural tube during neurulation in all-trans retinoic acid (atRA)-induced spina bifida in fetal rats. Cell apoptosis was assessed by TUNEL assay on whole-mount and serially sectioned samples of rat embryos with spina bifida. Cell proliferation of lumbo-sacral neural progenitor cells was assessed by staining for the mitotic marker Ki67 and pH3. We found an excess of apoptosis in the neuroepithelium of embryos with spina bifida, which became more marked as embryos progress from E11 to E13. Conversely, there was a reduction in cell proliferation in spina bifida embryos, with a progressively greater difference from controls with stage from E11 to 13. Thus, atRA-induced spina bifida in rat shows perturbed apoptosis and proliferation of neural progenitors in the lumbo-sacral spinal cord during embryonic development, which might contribute to the pathogenesis of spina bifida. (c) 2012 ISDN. Published by Elsevier Ltd. All rights reserved.