Sma- and Mad-related Protein 7 (Smad7) Is Required for Embryonic Eye Development in the Mouse*
Sma- and Mad-related Protein 7 (Smad7) Is Required for Embryonic Eye Development in the Mouse*
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DOI：
10.1074/jbc.m112.416719
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发表时间：
2013-02
期刊：
影响因子：
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通讯作者：
Rui Zhang;Heng Huang;P. Cao;Zhenzhen Wang;Yan Chen;Yi Pan
中科院分区：
文献类型：
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作者：
Rui Zhang;Heng Huang;P. Cao;Zhenzhen Wang;Yan Chen;Yi Pan
背景：目前尚不清楚Smad7在眼睛发育中是否具有功能作用。结果：Smad7基因缺失的小鼠眼睛发育有缺陷，并伴随着BMP信号、眼周间充质基因和声波刺激物信号模式的改变。结论：Smad7对小鼠的眼睛发育是不可或缺的。意义：Smad7是眼睛发育所必需的。Smad7是一种细胞内抑制蛋白，可拮抗转化生长因子-β家族成员的信号转导。小鼠体内Smad7基因缺失会导致心脏发育异常。然而，Smad7在其他器官的发育中是否具有功能作用一直是个未知数。在这里，我们提供的证据表明，Smad7在小鼠的眼睛发育中发挥了作用。Smad7在发育中的胚胎眼的晶状体和视网膜中都有表达。Smad7缺失可引起不同程度的眼球缺陷症和小眼球，并伴有细胞凋亡和增殖的改变。Smad7与晶状体分化有关，但不是诱导晶状体胎盘所必需的。Bmp7和Pitx2基因表达下调可延缓突变小鼠眼周间充质的发育。Smad7缺失影响视网膜的空间构型，并伴随着骨形态发生蛋白(BMP)信号的改变。在妊娠晚期，转化生长因子-β信号在分化的视网膜中表达上调。Smad7突变小鼠视盘扩张，声学刺猬(SHH)信号增强。此外，Smad7的缺失导致视网膜神经发生的时间变化。总而言之，我们的研究表明，Smad7对眼睛发育是必不可少的。此外，我们的数据表明，BMP、转化生长因子-β和SHH信号的改变可能是Smad7缺失导致眼睛发育缺陷的原因。
Background: Currently it is unknown whether Smad7 has a functional role in eye development. Results: Eye development is defective in Smad7 null mice and is accompanied by alterations in the patterning of BMP signals, periocular mesenchymal genes, and sonic hedgehog signaling. Conclusion: Smad7 is indispensable for eye development in the mouse. Significance: Smad7 is required for eye development. Smad7 is an intracellular inhibitory protein that antagonizes the signaling of TGF-β family members. Deletion of Smad7 in the mouse leads to an abnormality in heart development. However, whether Smad7 has a functional role in the development of other organs has been elusive. Here we present evidence that Smad7 imparts a role to eye development in the mouse. Smad7 is expressed in both the lens and retina in the developing embryonic eye. Depletion of Smad7 caused various degrees of coloboma and microphthalmia with alterations in cell apoptosis and proliferation in eyes. Smad7 was implicated in lens differentiation but was not required for the induction of the lens placode. The development of the periocular mesenchyme was retarded with the down-regulation of Bmp7 and Pitx2 in mutant mice. Retinal spatial patterning was affected by Smad7 deletion and was accompanied by altered bone morphogenetic protein (BMP) signaling. At late gestation stages, TGF-β signaling was up-regulated in the differentiating retina. Smad7 mutant mice displayed an expanded optic disc with increasing of sonic hedgehog (SHH) signaling. Furthermore, loss of Smad7 led to a temporal change in retinal neurogenesis. In conclusion, our study suggests that Smad7 is essential for eye development. In addition, our data indicate that alterations in the signaling of BMP, TGF-β, and SHH likely underlie the defects in eye development caused by Smad7 deletion.