Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Differentiation
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Bone Morphogenetic Protein 7
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism
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Cell Division
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Crosses, Genetic
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DNA-Binding Proteins / biosynthesis
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Embryonic Induction*
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Epithelium
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Eye Proteins
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Forkhead Transcription Factors
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Genes, Reporter
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HMGB Proteins
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Homeodomain Proteins / biosynthesis
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Homeodomain Proteins / genetics
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Lens, Crystalline / embryology*
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Mice
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Mice, Transgenic
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Models, Genetic
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Nuclear Proteins / biosynthesis
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PAX6 Transcription Factor
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Paired Box Transcription Factors
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Receptors, Fibroblast Growth Factor / antagonists & inhibitors
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Receptors, Fibroblast Growth Factor / genetics
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Receptors, Fibroblast Growth Factor / metabolism*
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Repressor Proteins
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SOXB1 Transcription Factors
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Signal Transduction
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Transcription Factors / metabolism
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Transforming Growth Factor beta*
Substances
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Antigens, Differentiation
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Bone Morphogenetic Protein 7
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Bone Morphogenetic Proteins
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DNA-Binding Proteins
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Eye Proteins
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Forkhead Transcription Factors
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Foxe3 protein, mouse
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HMGB Proteins
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Homeodomain Proteins
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Nuclear Proteins
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PAX6 Transcription Factor
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Paired Box Transcription Factors
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Pax6 protein, mouse
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Peptide Fragments
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Receptors, Fibroblast Growth Factor
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Repressor Proteins
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SOXB1 Transcription Factors
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Sox2 protein, mouse
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Transcription Factors
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Transforming Growth Factor beta