Functional mode of FoxD1/CBF2 for the establishment of temporal retinal specificity in the developing chick retina
Functional mode of FoxD1/CBF2 for the establishment of temporal retinal specificity in the developing chick retina
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DOI：
10.1016/j.ydbio.2009.05.549
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发表时间：
2009-07-15
影响因子：
2.7
通讯作者：
Noda, Masaharu
中科院分区：
文献类型：
--
作者：
Takahashi, Hiroo;Sakuta, Hiraki;Noda, Masaharu
两个翼螺旋转录因子FoxG1（以前称为小鸡脑因子1，CBF1）和FoxD1（小鸡脑因子2，CBF2）分别在发育中的小鸡视网膜的鼻区和颞区特异性表达。我们之前证明FoxG1控制包括FoxD1在内的地形分子的表达，并决定鼻视网膜的区域特异性。已知17601具有时间特异性，然而，分子机制和下游靶点尚未阐明。在这里，我们讨论了利用卵内电穿孔技术在发育中的视网膜中建立时间特异性的遗传机制。成纤维细胞生长因子（Fibroblast growth factor, Fgf）和Wnt首先在诱导视神经泡中FoxG1和FoxD1的区域特异性表达中起关键作用。FoxD1错表达可抑制FoxG1、GH6、SOHo1和ephrin-A5的表达，并诱导EphA3在视网膜中的表达。GH6和SOHo1抑制FoxD1的表达。与FoxG1对骨形态发生蛋白（BMP）信号传导的抑制作用相反，FoxD1不会改变BMP4或BMP2的表达。对FoxD1嵌合突变体的研究表明，FoxD1作为一种转录抑制因子，控制其在视网膜中的下游靶标。结合之前的研究结果，我们的数据表明FoxG1和FoxD1位于视网膜鼻颞轴区域特异性基因级联的顶端，FoxD1决定了颞特异性。(C) 2009爱思唯尔公司版权所有。
Two winged-helix transcription factors, FoxG1 (previously called chick brain factor1, CBF1) and FoxD1 (chick brain factor2, CBF2), are expressed specifically in the nasal and temporal regions of the developing chick retina, respectively. We previously demonstrated that FoxG1 controls the expression of topographic molecules including FoxD1, and determines the regional specificity of the nasal retina. 17601 is known to prescribe temporal specificity, however, molecular mechanisms and downstream targets have not been elucidated. Here we addressed the genetic mechanisms for establishing temporal specificity in the developing retina using an in ovo electroporation technique. Fibroblast growth factor (Fgf) and Wnt first play pivotal roles in inducing the region-specific expression of FoxG1 and FoxD1 in the optic vesicle. Misexpression of FoxD1 represses the expression of FoxG1, GH6, SOHo1, and ephrin-A5, and induces that of EphA3 in the retina. GH6 and SOHo1 repress the expression of FoxD1. In contrast to the inhibitory effect of FoxG1 on bone morphogenic protein (BMP) signaling, FoxD1 does not alter the expression of BMP4 or BMP2. Studies with chimeric mutants of FoxD1 showed that FoxD1 acts as a transcription repressor in controlling its downstream targets in the retina. Taken together with previous findings, our data suggest that FoxG1 and FoxD1 are located at the top of the gene cascade for regional specification along the nasotemporal (anteroposterior) axis in the retina, and FoxD1 determines temporal specificity. (C) 2009 Elsevier Inc. All rights reserved.