AIM:To explore the molecular mechanisms in lens development and the pathogenesis of Peters anomaly in Smad4 defective mice.METHODS:Le-Cre transgenic mouse line was employed to inactivate Smad4 in the surface ectoderm ...AIM:To explore the molecular mechanisms in lens development and the pathogenesis of Peters anomaly in Smad4 defective mice.METHODS:Le-Cre transgenic mouse line was employed to inactivate Smad4 in the surface ectoderm selectively.Pathological techniques were used to reveal the morphological changes of the anterior segment in Smad4 defective eye.Immunohistochemical staining was employed to observe the expression of E-cadherin,Ncadherin and a-SMA in anterior segment of Smad4 defective mice and control mice at embryonic(E) day 16.5.Real-time quantitative polymerase chain reaction(qPCR) was performed to detect the expression of Snail,Zeb1,Zeb2 and Twist2 in lens of Smad4 defective mice and control mice at E16.5.RESULTS:Conditional deletion of Smad4 on eye surface ectoderm resulted in corneai dysplasia,iridocorneal angle closure,corneolenticular adhesions and cataract resembling Peters anomaly.Loss of Smad4 function inhibited E-cadherin expression in the lens epithelium cells and corneai epithelium cells in Smad4 defective eye.Expression of N-cadherin was upregulated in corneai epithelium and corneai stroma.Both E-cadherin and N-cadherin were down-regulated at the future trabecular meshwork region in mutant eye.The qPCR results showed that the expression of Twist2 was increased significantly in the mutant lens(P<0.01).CONCLUSION:Smad4 is essential to eye development and likely a candidate pathogenic gene to Peters anomaly by regulating epithelial-mesenchymal transition.Twist2 can be regulated by Smad4 and plays an essential role in lens development.展开更多
基金Supported by the National Natural Science Foundation of China(No.81470617No.81371003)Colleges and Universities Scientific Research Project of Liaoning Province,China(No.L2014305)
文摘AIM:To explore the molecular mechanisms in lens development and the pathogenesis of Peters anomaly in Smad4 defective mice.METHODS:Le-Cre transgenic mouse line was employed to inactivate Smad4 in the surface ectoderm selectively.Pathological techniques were used to reveal the morphological changes of the anterior segment in Smad4 defective eye.Immunohistochemical staining was employed to observe the expression of E-cadherin,Ncadherin and a-SMA in anterior segment of Smad4 defective mice and control mice at embryonic(E) day 16.5.Real-time quantitative polymerase chain reaction(qPCR) was performed to detect the expression of Snail,Zeb1,Zeb2 and Twist2 in lens of Smad4 defective mice and control mice at E16.5.RESULTS:Conditional deletion of Smad4 on eye surface ectoderm resulted in corneai dysplasia,iridocorneal angle closure,corneolenticular adhesions and cataract resembling Peters anomaly.Loss of Smad4 function inhibited E-cadherin expression in the lens epithelium cells and corneai epithelium cells in Smad4 defective eye.Expression of N-cadherin was upregulated in corneai epithelium and corneai stroma.Both E-cadherin and N-cadherin were down-regulated at the future trabecular meshwork region in mutant eye.The qPCR results showed that the expression of Twist2 was increased significantly in the mutant lens(P<0.01).CONCLUSION:Smad4 is essential to eye development and likely a candidate pathogenic gene to Peters anomaly by regulating epithelial-mesenchymal transition.Twist2 can be regulated by Smad4 and plays an essential role in lens development.
