Inactivation of Smad4 leads to impaired ocular development and cataract formation.
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.
Liu
Ying
Y
Department of Ophthalmology and Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. yingliu@doheny.org
Kawai
Kirio
K
Khashabi
Shabnam
S
Deng
Chuxia
C
Liu
Yi-Hsin
YH
Yiu
Samuel
S
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
D000199:Actins; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D038201:alpha-Crystallins; D038204:beta-Crystallins