Control of lens development by Lhx2-regulated neuroretinal FGFs

被引：15

作者：

Thein, Thuzar ^{[1
]}

de Melo, Jimmy ^{[1
]}

Zibetti, Cristina ^{[1
]}

Clark, Brian S. ^{[1
]}

Juarez, Felicia ^{[1
]}

Blackshaw, Seth ^{[1
,2
,3
,4
,5
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, 733 N Broadway, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, 733 N Broadway, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurol, 733 N Broadway, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Ctr Human Syst Biol, 733 N Broadway, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Inst Cell Engn, 733 N Broadway, Baltimore, MD 21205 USA

来源：

DEVELOPMENT | 2016年 / 143卷 / 21期

基金：

美国国家卫生研究院;

关键词：

FGF; Genetics; Lens; Mouse; Retina; Transcription factor; FIBROBLAST-GROWTH-FACTOR; MOUSE RETINAL DEVELOPMENT; FIBER DIFFERENTIATION; CELL-DIFFERENTIATION; RECEPTOR SPECIFICITY; EYE DEVELOPMENT; NEURAL RETINA; FACTOR FAMILY; BMP SIGNALS; EXPRESSION;

D O I：

10.1242/dev.137760

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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; Lhx2(lox/lox) mice, 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/lox mice, 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.

引用

页码：3994 / 4002

页数：9

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