title: Anterior segment dysgenesis correlation with epithelial-mesenchymal transition in Smad4 knockout mice.
abstract: OBJECTIVE
  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, N-cadherin and α-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. Statistical evaluations were performed using the unpaired Student's t-test (two-tailed) by SPSS 11.0 software.
  
  
  RESULTS
  Conditional deletion of Smad4 on eye surface ectoderm resulted in corneal 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 corneal epithelium cells in Smad4 defective eye. Expression of N-cadherin was up-regulated in corneal epithelium and corneal 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).
  
  
  CONCLUSIONS
  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.
authors: Department of Ophthalmology, the Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang 110005, Liaoning Province, China.
authors: Jing
authors: J
authors: Li
authors: Department of Ophthalmology, the Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang 110005, Liaoning Province, China.
authors: Yu
authors: Y
authors: Qin
authors: Department of Ophthalmology, the Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang 110005, Liaoning Province, China.
authors: Fang-Kun
authors: FK
authors: Zhao
authors: The Shenyang Fourth People's Hospital, Shenyang Eye Research Institute, Shenyang 110005, Liaoning Province, China.
authors: Di
authors: D
authors: Wu
authors: Department of Ophthalmology, Ningbo No.2 Hospital, Ningbo 315010, Zhejiang Province, China.
authors: Xue-Fei
authors: XF
authors: He
authors: Department of Ophthalmology, the Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang 110005, Liaoning Province, China.
authors: Jia
authors: J
authors: Liu
authors: Department of Ophthalmology, the Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang 110005, Liaoning Province, China.
authors: Jiang-Yue
authors: JY
authors: Zhao
authors: Department of Ophthalmology, the Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang 110005, Liaoning Province, China.
authors: Jin-Song
authors: JS
authors: Zhang
keywords: N-cadherin; Peters anomaly; Smad4; Twist2; anterior segment dysgenesis