Pax6 controls the proliferation rate of neuroepithelial progenitors from the mouse optic vesicle
Pax6 controls the proliferation rate of neuroepithelial progenitors from the mouse optic vesicle
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DOI：
10.1016/j.ydbio.2006.11.006
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发表时间：
2007-01-15
影响因子：
2.7
通讯作者：
Bernier, Gilbert
中科院分区：
文献类型：
--
作者：
Duparc, Robert-Hugues;Abdouh, Mohamed;Bernier, Gilbert
在脊椎动物中，有限数量的同源异型盒转录因子在视泡原基中表达，是形成眼睛所必需的，也是足够的。目前，人们对这些因子在视泡生长中的不同作用以及该器官中主要神经上皮细胞(NE)前体细胞的性质知之甚少。我们已经鉴定了小鼠视泡中存在的多潜能细胞群，它显示出广泛的增殖潜力，并在体外表达NE祖细胞和视网膜标志物。在形成视泡的Pax6突变胚胎中，我们发现常驻的NE祖细胞数量多于正常。在体外，Pax6缺失的NE前体细胞过度增殖，表现为p16(Inkα)、p19(Arf)、p27(Kip1)、p57(Kip2)和p21(Cip1)表达降低。Pax6过表达抑制细胞增殖和次级集落形成，支持Pax6对去甲肾上腺素前体细胞周期自主作用的假说。值得注意的是，这些体外数据与在早期Pax6突变体的视泡中观察到的有丝分裂的异常数量有关，与Pax6与p27(Kip1)启动子区域上游的染色质相关，以及与Pax6突变体原始前脑中p27(Kip1)、p57(Kip2)和p21(Cip1)的表达水平降低有关。综上所述，我们的结果表明，在视网膜前体细胞识别和神经发生之前，Pax6需要调节存在于小鼠视泡中的NE前体细胞的增殖率。(C)2006 Elsevier Inc.保留所有权利。
In vertebrates, a limited number of homeobox-containing transcription factors are expressed in the optic vesicle primordium and are required and sufficient for eye formation. At present, little is known about the distinct functions of these factors in optic vesicle growth and on the nature of the main neuroepithelial (NE) progenitor population present in this organ. We have characterized a multipotent cell population present in the mouse optic vesicle that shows extensive proliferation potential and which expresses NE progenitor and retinal markers in vitro. In Pax6 mutant embryos, which form an optic vesicle, we found that the number of resident NE progenitors was greater than normal. In vitro, Pax6-null NE progenitors overproliferate and display reduced P16(Ink alpha), p19(Arf), p27(kip1), p57(kip2), and p21(cip1) expression. Pax6 overexpression repressed cellular proliferation and secondary colonies formation, supporting the hypothesis that Pax6 acts cell-autonomously on NE progenitors cell cycle. Notably, these in vitro data correlated with aberrant numbers of mitosis observed in the optic vesicle of early stage Pax6 mutants, with Pax6 association with the chromatin upstream of p27(kip1) promoter region, and with reduced expression levels of p27(kip1), p57(kip2), and p21(cip1) in the primitive forebrain of Pax6 mutants. Taken together, our results suggest that, prior to retinal progenitor cell identity and neurogenesis, Pax6 is required to regulate the proliferation rate of NE progenitors present in the mouse optic vesicle. (c) 2006 Elsevier Inc. All rights reserved.