Fgf receptor signaling plays a role in lens induction

We describe experiments showing that fibroblast growth factor receptor (Fgf r) signaling plays a role in lens induction. Three distinct experimental st rategies were used: (1) using small-molecule inhibitors of Fgfr kinase acti vity, 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) th at expressed a dominant-negative Fgf receptor exclusively in the presumptiv e 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 tran sgenic and Bmp7-null mice, we showed that there is a genetic interaction be tween 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 inducti on. This analysis establishes a role for Fgfr signaling in lens induction a nd defines a genetic pathway in which Fgfr and Bmp7 signaling converge on P ax6 expression in the lens placode with the Foxe3 and Sox2 genes lying down stream.