Maeda Atsuko, Moriguchi Takashi, Hamada Michito, Kusakabe Manabu, Fujioka Yuki, Nakano Takako, Yoh Keigyou, Lim Kim-Chew, Engel James Douglas, Takahashi Satoru
Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan.
Dev Dyn. 2009 Sep;238(9):2280-91. doi: 10.1002/dvdy.22035.
During vertebrate lens development, the anterior, ectoderm-derived lens vesicle cells differentiate into a monolayer of epithelial cells that retain proliferative potential. Subsequently, they exit the cell cycle and give rise to posterior lens fiber cells that form the lens body. In the present study, we demonstrate that the transcription factor GATA-3 is expressed in the posterior lens fiber cells during embryogenesis, and that GATA-3 deficiency impairs lens development. Interestingly, expression of E-cadherin, a premature lens vesicle marker, is abnormally prolonged in the posterior region of Gata3 homozygous mutant lenses. Furthermore, expression of gamma-crystallin, a differentiation marker for fiber cells, is reduced. This suppressed differentiation is accompanied by an abnormal cellular proliferation, as well as with diminished levels of the cell-cycle inhibitors Cdkn1b/p27 and Cdkn1c/p57 and increased Ccnd2/cyclin D2 abundance. Thus, these observations suggest that GATA-3 is essential for lens cells differentiation and proper cell cycle control.
在脊椎动物晶状体发育过程中，源自外胚层的前晶状体泡细胞分化为具有增殖潜能的单层上皮细胞。随后，它们退出细胞周期，产生形成晶状体主体的后晶状体纤维细胞。在本研究中，我们证明转录因子GATA-3在胚胎发生期间在后晶状体纤维细胞中表达，并且GATA-3缺陷会损害晶状体发育。有趣的是，E-钙黏蛋白（一种早熟晶状体泡标记物）的表达在Gata3纯合突变晶状体的后部区域异常延长。此外，纤维细胞分化标记物γ-晶状体蛋白的表达减少。这种分化抑制伴随着异常的细胞增殖，以及细胞周期抑制剂Cdkn1b/p27和Cdkn1c/p57水平降低和Ccnd2/细胞周期蛋白D2丰度增加。因此，这些观察结果表明GATA-3对于晶状体细胞分化和适当的细胞周期控制至关重要。
