Fgf receptor signaling plays a role in lens induction

• Published in: Development (Cambridge) Vol. 128; no. 22; pp. 4425 - 4438
• Main Authors: Faber, S C, Dimanlig, P, Makarenkova, H P, Shirke, S, Ko, K, Lang, R A
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 15.11.2001
• Subjects: Animals; Antigens, Differentiation; bmp7 gene; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; Cell Division; Crosses, Genetic; DNA-Binding Proteins - biosynthesis; Embryonic Induction; Epithelium; Eye Proteins; Forkhead Transcription Factors; Foxe3 gene; Genes, Reporter; HMGB Proteins; Homeodomain Proteins - biosynthesis; Homeodomain Proteins - genetics; Lens, Crystalline - embryology; Mice; Mice, Transgenic; Models, Genetic; Nuclear Proteins - biosynthesis; Paired Box Transcription Factors; Pax6 gene; PAX6 Transcription Factor; Peptide Fragments - genetics; Peptide Fragments - metabolism; Receptors, Fibroblast Growth Factor - antagonists & inhibitors; Receptors, Fibroblast Growth Factor - genetics; Receptors, Fibroblast Growth Factor - metabolism; Repressor Proteins; Signal Transduction; Sox2 gene; SOXB1 Transcription Factors; Tfr7 gene; Transcription Factors - metabolism; Transforming Growth Factor beta
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.128.22.4425

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.