title: Control of lens development by Lhx2-regulated neuroretinal FGFs.
abstract: Fibroblast growth factor (FGF) signaling is an essential regulator of lens epithelial cell proliferation and survival, as well as lens fiber cell differentiation. However, the identities of these FGF factors, their source tissue and the genes that regulate their synthesis are unknown. We have found that Chx10-Cre;Lhx2lox/loxmice, which selectively lack Lhx2 expression in neuroretina from E10.5, showed an early arrest in lens fiber development along with severe microphthalmia. These mutant animals showed reduced expression of multiple neuroretina-expressed FGFs and canonical FGF-regulated genes in neuroretina. When FGF expression was genetically restored in Lhx2-deficient neuroretina of Chx10-Cre;Lhx2lox/loxmice, we observed a partial but nonetheless substantial rescue of the defects in lens cell proliferation, survival and fiber differentiation. These data demonstrate that neuroretinal expression of Lhx2 and neuroretina-derived FGF factors are crucial for lens fiber development in vivo.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
authors.forename: Thuzar
authors.initials: T
authors.lastname: Thein
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: de Melo
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zibetti
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Clark
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
authors.forename: Felicia
authors.initials: F
authors.lastname: Juarez
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA sblack@jhmi.edu.|Department of Ophthalmology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.|Department of Neurology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.|Center for Human Systems Biology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.|Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
authors.forename: Seth
authors.identifier: 0000-0002-1338-8476
authors.initials: S
authors.lastname: Blackshaw
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004622:Embryo, Mammalian; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007908:Lens, Crystalline / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008850:Microphthalmos / Q000196:embryology / Q000235:genetics; D038081:Organogenesis / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D055351:Retinal Neurons / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; D005346:Fibroblast Growth Factors
keywords: FGF; Genetics; Lens; Mouse; Retina; Transcription factor