Ghai Kanika, Stanke Jennifer J, Fischer Andy J
Department of Neuroscience, The Ohio State University, College of Medicine and Public Health, 3020 Graves Hall, 333 W. 10th Ave, Columbus, OH 43210-1239, USA.
Brain Res. 2008 Feb 4;1192:76-89. doi: 10.1016/j.brainres.2007.01.105. Epub 2007 Feb 2.
A circumferential marginal zone (CMZ) of retinal progenitors has been identified in most vertebrate classes, with the exception of mammals. Little is known about the formation of the CMZ during late stages of embryonic retinal histogenesis. Thus, the purpose of this study was to characterize the formation and patterning of the CMZ in the embryonic chicken retina. We identified progenitors by assaying for the expression of proliferating cell nuclear antigen (PCNA), N-cadherin and the nestin-related filament transitin, and newly generated cells by using BrdU-birthdating. We found that there is a gradual spatial restriction of progenitors into a discreet CMZ during late stages of embryonic development between E16 and hatching, at about E21. In addition, we found that retinal neurons remain immature for prolonged periods of time in far peripheral regions of the retina. Early markers of neuronal differentiation (such as HuC/D, calretinin and visinin) are expressed by neurons that are found directly adjacent to the CMZ. By contrast, genes (protein kinase C, calbindin, red/green opsin) that are expressed with a delay (7-10 days) after terminal mitosis in the central retina are not expressed until as many as 30 days after terminal mitosis in the far peripheral retina. We conclude that the neurons that are generated by late-stage CMZ progenitors differentiate much more slowly than neurons generated during early stages of retinal development. We propose that the microenvironment within the far peripheral retina at late stages of development permits the maintenance of a zone of progenitors and slows the differentiation of neurons.
除哺乳动物外,在大多数脊椎动物类别中都已发现视网膜祖细胞的圆周边缘区(CMZ)。关于胚胎视网膜组织发生后期CMZ的形成知之甚少。因此,本研究的目的是描述胚胎鸡视网膜中CMZ的形成和模式。我们通过检测增殖细胞核抗原(PCNA)、N-钙黏蛋白和巢蛋白相关细丝转甲状腺素蛋白的表达来鉴定祖细胞,并使用BrdU标记法来鉴定新生成的细胞。我们发现,在胚胎发育后期E16至孵化(约E21)期间,祖细胞逐渐在空间上限制为一个离散的CMZ。此外,我们发现视网膜神经元在视网膜的远周边区域长时间保持不成熟状态。神经元分化的早期标志物(如HuC/D、钙视网膜蛋白和视锥蛋白)由紧邻CMZ的神经元表达。相比之下,在视网膜中央终末有丝分裂后延迟(7-10天)表达的基因(蛋白激酶C、钙结合蛋白、红/绿视蛋白)在视网膜远周边区域直到终末有丝分裂后多达30天才表达。我们得出结论,晚期CMZ祖细胞产生的神经元比视网膜发育早期产生的神经元分化要慢得多。我们提出,发育后期视网膜远周边区域的微环境允许祖细胞区的维持并减缓神经元的分化。