近日，国际杂志《生物化学杂志》（Journal of Biological Chemistry）在线发表了中科院上海生科院营养科学研究所陈雁研究组的最新研究进展：“Sma- and mad- related protein 7 (Smad7) is required for embryonic eye development in the mouse”，在文中，研究者首次揭示了Smad7在胚胎眼部发育过程中具有重要作用。
Smad7是TGF-b信号通路的一个抑制因子。Smad7活性失调与人类多种疾病相关。陈雁研究员带领的研究组成员在前期的研究工作中发现，在胚胎发育过程中，Smad7通过调节TGF-b信号强度，影响心脏流出道的形成和重塑，以及心肌细胞的正常功能。但目前尚不清楚Smad7是否调节其它器官的发育。
在这一研究中，博士生张蕊和潘怡副研究员等人首次发现了Smad7在胚胎期眼部发育过程具有重要作用。研究发现，Smad7在胚胎眼部组织中广泛表达。小鼠体内敲除Smad7导致不同程度的眼睛缺损和小眼症，同时伴随眼部细胞凋亡和增值的异常。进一步研究发现，Smad7参与了晶状体的分化。同时，在小鼠中敲除Smad7造成眼外周间质细胞发育迟缓，视盘区域扩展，视网膜空间形态异常以及视网膜神经生成延滞。
BMP和TGF-b信号通路在特定发育时期的改变，以及SHH信号通路的上调可能是导致上述现象出现的原因。该研究揭示了Smad7通过影响不同空间定位的转录因子和信号通路影响小鼠胚胎的眼部发育，为研究TGF-b超家族成员在器官发育的重要作用提供了新的依据。
该项研究受到中科院、国家基金委和科技部项目的支持。（生物谷Bioon.com）
doi:10.1074/jbc.M112.416719
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Sma- and Mad-related protein 7 (Smad7) is required for embryonic eye development in the mouse.
Zhang R, Huang H, Cao P, Wang Z, Chen Y, Pan Y.
Smad7 is an intracellular inhibitory protein that antagonizes the signaling of TGF-b family members. Deletion of Smad7 in mouse leads to abnormality in heart development. However, whether Smad7 has a functional role to 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 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 the lens differentiation but not required for the induction of the lens placode. The development of the periocular mensychlyma was retarded with downregulation of Bmp7 and Pitx2 in the mutant mice. Retinal spatial patterning was affected by Smad7 deletion, accompanied by altered BMP signaling. At late gestation stages, TGF-b signaling was upregulated 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 temporal change of 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-b and SHH likely underlie the defects of eye development caused by Smad7 deletion.
