近日，國際雜志《生物化學(xué)雜志》（Journal of Biological Chemistry）在線發(fā)表了中科院上海生科院營養(yǎng)科學(xué)研究所陳雁研究組的最新研究進展：“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在胚胎眼部發(fā)育過程中具有重要作用,。
Smad7是TGF-b信號通路的一個抑制因子。Smad7活性失調(diào)與人類多種疾病相關(guān),。陳雁研究員帶領(lǐng)的研究組成員在前期的研究工作中發(fā)現(xiàn),，在胚胎發(fā)育過程中，Smad7通過調(diào)節(jié)TGF-b信號強度,，影響心臟流出道的形成和重塑,，以及心肌細(xì)胞的正常功能。但目前尚不清楚Smad7是否調(diào)節(jié)其它器官的發(fā)育,。
在這一研究中,，博士生張蕊和潘怡副研究員等人首次發(fā)現(xiàn)了Smad7在胚胎期眼部發(fā)育過程具有重要作用。研究發(fā)現(xiàn),，Smad7在胚胎眼部組織中廣泛表達(dá),。小鼠體內(nèi)敲除Smad7導(dǎo)致不同程度的眼睛缺損和小眼癥，同時伴隨眼部細(xì)胞凋亡和增值的異常,。進一步研究發(fā)現(xiàn),，Smad7參與了晶狀體的分化。同時,，在小鼠中敲除Smad7造成眼外周間質(zhì)細(xì)胞發(fā)育遲緩,，視盤區(qū)域擴展，視網(wǎng)膜空間形態(tài)異常以及視網(wǎng)膜神經(jīng)生成延滯,。
BMP和TGF-b信號通路在特定發(fā)育時期的改變,，以及SHH信號通路的上調(diào)可能是導(dǎo)致上述現(xiàn)象出現(xiàn)的原因。該研究揭示了Smad7通過影響不同空間定位的轉(zhuǎn)錄因子和信號通路影響小鼠胚胎的眼部發(fā)育,，為研究TGF-b超家族成員在器官發(fā)育的重要作用提供了新的依據(jù),。
該項研究受到中科院、國家基金委和科技部項目的支持,。（生物谷Bioon.com）
doi:10.1074/jbc.M112.416719
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PMID:
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.
