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Fgf receptor signaling plays a role in lens induction

Sonya C. Faber, Patricia Dimanlig, Helen P. Makarenkova, Sanjay Shirke, Kyung Ko and Richard A. Lang^*,

Skirball Institute for Biomolecular Medicine, Developmental Genetics Program, Cell Biology and Pathology Departments, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA
^* Present address: Divisions of Developmental Biology and Ophthalmology, Children’s Hospital Research Foundation, 3333 Burnett Avenue, Cincinnati, OH 45229-3039, USA

Author for correspondence (e-mail: richard.lang{at}chmcc.org)

Accepted August 20, 2001

We describe experiments showing that fibroblast growth factor receptor (Fgfr) signaling plays a role in lens induction. Three distinct experimental strategies were used: (1) using small-molecule inhibitors of Fgfr kinase activity, we showed that both the transcription level and protein expression of Pax6, a transcription factor critical for lens development, was diminished in the presumptive lens ectoderm; (2) transgenic mice (designated Tfr7) that expressed a dominant-negative Fgf receptor exclusively in the presumptive lens ectoderm showed defects in formation of the lens placode at E9.5 but in addition, showed reduced levels of expression for Pax6, Sox2 and Foxe3, all markers of lens induction; (3) by performing crosses between Tfr7 transgenic and Bmp7-null mice, we showed that there is a genetic interaction between Fgfr and Bmp7 signaling at the induction phases of lens development. This manifested as exacerbated lens development defects and lower levels of Pax6 and Foxe3 expression in Tfr7/Tfr7, Bmp7^+/– mice when compared with Tfr7/Tfr7 mice alone. As Bmp7 is an established lens induction signal, this provides further evidence that Fgfr activity is important for lens induction. This analysis establishes a role for Fgfr signaling in lens induction and defines a genetic pathway in which Fgfr and Bmp7 signaling converge on Pax6 expression in the lens placode with the Foxe3 and Sox2 genes lying downstream.

Key words: Lens induction, Lens development, Dysgenetic lens, Pax6, Fgfr, Bmp7, Foxe3, Sox2, Mouse

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