PUBLICATION

FGF19 is a target for FOXC1 regulation in ciliary body derived cells

Authors
Tamimi, Y., Skarie, J.M., Footz, T., Berry, F.B., Link, B.A., and Walter, M.A.
ID
ZDB-PUB-060927-13
Date
2006
Source
Human molecular genetics   15(21): 3229-3240 (Journal)
Registered Authors
Link, Brian, Skarie, Jonathan M.
Keywords
none
MeSH Terms
  • Animals
  • Base Sequence
  • Cell Line
  • Chromatin Immunoprecipitation/methods
  • Ciliary Body/cytology
  • Fibroblast Growth Factors/genetics*
  • Forkhead Transcription Factors/genetics*
  • Gene Expression Regulation, Developmental
  • Glaucoma/genetics
  • Humans
  • MAP Kinase Signaling System
  • Molecular Sequence Data
  • Transfection
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
PubMed
17000708 Full text @ Hum. Mol. Genet.
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes