FGF19 is a target for FOXC1 regulation in ciliary body-derived cells. Hum Mol Genet 2006 Nov 01;15(21):3229-40
Date
09/27/2006Pubmed ID
17000708DOI
10.1093/hmg/ddl400Scopus ID
2-s2.0-33750216514 (requires institutional sign-in at Scopus site) 41 CitationsAbstract
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 MAAuthor
Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBase 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
