FGF4-Mediated Ectopic Lens Induction in Transgenic Mice

Abstract

Abstract: : Purpose: The lens is postulated to serve as an organizer for the eye. Organizer activities are assumed to originate in the lens epithelial cells. In order to test whether lens fiber cells also have organizer activity, we generated transgenic mice in which all the lens cells are converted to fiber cells from the outset of lens differentiation. Methods: A construct with the lens-specific Pax6 enhancer and the P0 Pax6 promoter linked to a cDNA encoding FGF4 was used to generate transgenic mice. A DREAM-lacZ construct was coinjected to allow X-gal staining of lens cells. Transgenic embryos were characterized for ocular changes by histology, in situ hybridization, and immunohistochemistry. Results: The transgenic mice showed a more dramatic phenotype than expected. The lens differentiation field was enlarged to include regions of the nasal placode and/or the future oral epithelium. Ectopic lenses were induced in the absence of ectopic neural retina. The lenses that formed from the normal lens placode regions migrated deeply into the peri-ocular mesenchyme and induced a reorientation of the neural retina. Corneal differentiation was lost. Conclusions: FGF4 expression can induce competent surface ectoderm to convert to a program of lens cell formation. Ectopic positioning of the lens leads to reorientation of the retina. These alterations in ocular development result in the loss of the corneal differentiation program.

Keywords: growth factors/growth factor receptors • transgenics/knock-outs • molecular biology