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FGF19 is a target for FOXC1 regulation in ciliary body-derived cells. Hum Mol Genet 2006 Nov 01;15(21):3229-40

Date

09/27/2006

Pubmed ID

17000708

DOI

10.1093/hmg/ddl400

Scopus ID

2-s2.0-33750216514   33 Citations

Abstract

The forkhead C1 (FOXC1) transcription factor is involved in the development and regulation of several organs, including the eye, where FOXC1 alterations cause iris, trabecular meshwork and corneal anomalies. Using nickel agarose chromatin enrichment with human anterior segment cells, we previously identified the fibroblast growth factor 19 (FGF19) locus as a gene potentially regulated by FOXC1. Here, we demonstrate that FGF19 is a direct target of FOXC1 in the eye. FOXC1 positively regulates FGF19 expression in corneal and periocular mesenchymal cells in cell culture and in zebrafish embryos. Through the FGFR4 tyrosine kinase, FGF19 promotes MAPK phosphorylation in the developing and mature cornea. During development, loss of either FOXC1 or FGF19 results in complementary, but distinct, anterior segment dysgeneses. This study reveals an important role for FOXC1 in the direct regulation of the FGF19-FGFR4-MAPK pathway to promote both the development and maintenance of anterior segment structures within the eye.

Author List

Tamimi Y, Skarie JM, Footz T, Berry FB, Link BA, Walter MA

Author

Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Cell Line
Chromatin Immunoprecipitation
Ciliary Body
Fibroblast Growth Factors
Forkhead Transcription Factors
Gene Expression Regulation, Developmental
Glaucoma
Humans
MAP Kinase Signaling System
Molecular Sequence Data
Transfection
Zebrafish
Zebrafish Proteins
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0