Inactivation of Smad4 leads to impaired ocular development and cataract formation

PurposeSignaling 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.MethodsUsing 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.ResultsInactivation 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.ConclusionsSmad4 is required for the development and maintenance of the lens in addition to the proper development of the cornea, eyelids, and retina.

Research highlights
► Inactivation of Smad4 caused disruption in the development of the anterior segment.
► Inactivation of Smad4 failed to disrupt early lens development.
► Smad4 controlled lens cell cycle and cell death processes.
► Smad4 may regulate actin stress fiber assembly and eyelid epithelial movement.