title: Inactivation of Smad4 leads to impaired ocular development and cataract formation.
abstract: OBJECTIVE
  Signaling by members of the TGFβ superfamily of molecules is essential for embryonic development and homeostasis. Smad4, a key intracellular mediator in TGFβ signaling, forms transcriptional activator complexes with Activin-, BMP-, and TGFβ-restricted Smad proteins. However, the functional role of Smad4 in controlling different visual system compartments has not been fully investigated.
  
  
  METHODS
  Using the Pax6 promoter-driven Cre transgenic, smad4 was conditionally inactivated in the lens, cornea and ectoderm of the eyelids. Standard histological and molecular analytical approaches were employed to reveal morphological and cellular changes.
  
  
  RESULTS
  Inactivation of Smad4 in the lens led to microphthalmia and cataract formation in addition to the persistent adhesion of the retina to the lens and the iris to the cornea. Inactivation of Smad4 from the ectoderm of the eyelid and cornea caused disruption to eyelid fusion and proper development of the corneal epithelium and corneal stroma.
  
  
  CONCLUSIONS
  Smad4 is required for the development and maintenance of the lens in addition to the proper development of the cornea, eyelids, and retina.
authors.affiliation: Department of Ophthalmology and Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. yingliu@doheny.org
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Kirio
authors.initials: K
authors.lastname: Kawai
authors.forename: Shabnam
authors.initials: S
authors.lastname: Khashabi
authors.forename: Chuxia
authors.initials: C
authors.lastname: Deng
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Liu
authors.forename: Samuel
authors.initials: S
authors.lastname: Yiu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002386:Cataract / Q000235:genetics*; D049109:Cell Proliferation; D005124:Eye Abnormalities / Q000235:genetics*; D005143:Eyelids / Q000378:metabolism / Q000502:physiology; D007908:Lens, Crystalline / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D051901:Smad4 Protein / Q000235:genetics* / Q000378:metabolism; D038201:alpha-Crystallins / Q000096:biosynthesis; D038204:beta-Crystallins / Q000096:biosynthesis
chemical_list: D000199:Actins; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D038201:alpha-Crystallins; D038204:beta-Crystallins