title: Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development.
abstract: Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular surface ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on surface lens ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular surface ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular surface ectoderm may affect retinal 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, Liaoning Province, China.
authors: Jing
authors: J
authors: Li
authors: Department of Cell & Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America.|Department of Ophthalmology, Tulane University, New Orleans, Louisiana, United States of America.
authors: Shusheng
authors: S
authors: Wang
authors: Department of Cell & Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America.
authors: Chastain
authors: C
authors: Anderson
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, Liaoning Province, China.
authors: Fangkun
authors: F
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, Liaoning Province, China.
authors: Yu
authors: Y
authors: Qin
authors: Shenyang Fourth People's Hospital, Shenyang Eye Research Institute, Shenyang, Liaoning Province, China.
authors: Di
authors: D
authors: Wu
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, Liaoning Province, China.
authors: Xinwei
authors: X
authors: Wu
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, Liaoning Province, China.
authors: Jia
authors: J
authors: Liu
authors: Department of Ophthalmology, Ningbo No.2 Hospital, Ningbo, Zhejiang Province, China.
authors: Xuefei
authors: X
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, Liaoning Province, China.
authors: Jiangyue
authors: J
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, Liaoning Province, China.
authors: Jinsong
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D004475:Ectoderm / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008850:Microphthalmos / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D009419:Nerve Tissue Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D015792:Retinal Dysplasia / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D051901:Smad4 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
chemical_list: C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D051901:Smad4 Protein; D051153:Wnt Proteins; C492031:Wnt2b protein, mouse; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3