CONTROL OF CORNEAL ENDOTHELIUM DEVELOPMENT IN THE MOUSE
小鼠角膜内皮发育的控制
基本信息
- 批准号:6530102
- 负责人:
- 金额:$ 3.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-09-01 至 2003-07-31
- 项目状态:已结题
- 来源:
- 关键词:Mus musculus biological signal transduction cadherins cell differentiation cell migration corneal endothelium electron microscopy electrophysiology embryo /fetus tissue /cell culture embryogenesis epidermal growth factor gene expression growth factor receptors histogenesis immunocytochemistry in situ hybridization lens mesenchyme mutant neural crest polymerase chain reaction protein structure function subtraction hybridization transcription factor transforming growth factors
项目摘要
The goal of this study is to define the role of Mf1, a forehead/winged helix transcription factor, in the development of the cornea of the mammalian eye. We have previously shown that in mouse embryos lacking a functional Mf1 gene (generated either by homologous recombination-Mf1/lacZ-or as a result of spontaneous mutation-Mf1/Ch) the corneal endothelium fails to differentiate from the embryonic corneal mesenchyme. This is accompanied by a number of other eve developmental abnormalities, including failure of anterior chamber formation, iris dystrophy, and abnormalities of the trabecular meshwork (Kidson et al, 1999, Appendix). The failure to form a corneal endothelium in these mutants thus provides an ideal system for investigate the normal development of the corneal endothelium in vivo, about which little is known. The human homologue of the mouse Mf1 gene (known as FKHL/FREAC3) has recently been cloned by two groups. Dominant mutations in this gene have been shown to be associated with inherited anterior segment defects, including hypoplasia of the iris, dysgenesis of the anterior angle and trabecular meshwork, corneal opacity and increased risk of juvenile onset congenital glaucoma (Axenfeld-Rieger Anomaly, Mears et al, 1998: Nishimura et al, 1998). In addition, several inherited disorders of the cornea have been reported to humans. For example, congenital hereditary endothelial dystrophy, a condition that can be either autosomal dominant or recessive, is associated with absence of the endothelium, thickening of the stroma and corneal opacity (Mullany et al, 1995: Kirkness et al, 1987). Thus, the proposed studies will lead to a better understanding of human eye defects associated with corneal endothelium failure, including glaucoma and corneal endothelial dystrophy. The hypothesis will be tested that Mf1 functions in the corneal mesenchyme as part of the downstream signaling pathway from as yet unidentified factors secreted by the embryonic lens. The techniques to be used will include in vitro culture and differentiation of normal and mutant corneal mesenchyme, co-culture with embryonic lens, addition of growth factors, and screening for Mf1 regulated genes.
本研究的目的是确定Mf1(一种前额/翼螺旋转录因子)在哺乳动物眼睛角膜发育中的作用。我们之前已经证明,在缺乏功能性Mf1基因(通过同源重组-Mf1/ lacz或自发突变-Mf1/Ch产生)的小鼠胚胎中,角膜内皮不能从胚胎角膜间质分化。这伴随着许多其他的发育异常,包括前房形成失败、虹膜营养不良和小梁网异常(Kidson et al, 1999,附录)。因此,这些突变体不能形成角膜内皮,为研究角膜内皮在体内的正常发育提供了一个理想的系统,而我们对角膜内皮的正常发育知之甚少。小鼠Mf1基因的人类同源基因(称为FKHL/FREAC3)最近已被两个小组克隆出来。该基因的显性突变已被证明与遗传性前段缺陷相关,包括虹膜发育不全、前角和小梁网发育不良、角膜不透明和青少年先天性青光眼风险增加(Axenfeld-Rieger异常,Mears等人,1998;Nishimura等人,1998)。此外,一些遗传性角膜疾病已被报道给人类。例如,先天性遗传性内皮细胞营养不良(一种常染色体显性或隐性的疾病)与内皮细胞缺失、基质增厚和角膜混浊有关(Mullany et al ., 1995; Kirkness et al ., 1987)。因此,所提出的研究将有助于更好地了解与角膜内皮衰竭相关的人眼缺陷,包括青光眼和角膜内皮营养不良。这一假设将被验证,即Mf1在角膜间质中作为下游信号通路的一部分,从胚胎晶状体分泌的尚未确定的因素中发挥作用。使用的技术将包括正常和突变角膜间质的体外培养和分化,与胚胎晶状体共培养,添加生长因子,以及筛选Mf1调节基因。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Molecular events in early development of the ciliary body: a question of folding.
睫状体早期发育中的分子事件:折叠问题。
- DOI:10.1016/j.exer.2006.07.012
- 发表时间:2007
- 期刊:
- 影响因子:3.4
- 作者:Napier,HRL;Kidson,SH
- 通讯作者:Kidson,SH
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Christopher V Wright其他文献
Christopher V Wright的其他文献
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{{ truncateString('Christopher V Wright', 18)}}的其他基金
Control of endocrine pancreatic beta-cell fate, function, and proliferation
控制内分泌胰腺 β 细胞的命运、功能和增殖
- 批准号:
10359799 - 财政年份:2018
- 资助金额:
$ 3.2万 - 项目类别:
Architecture and communication controlling the efficient generation of beta cells
控制β细胞有效生成的架构和通信
- 批准号:
8316317 - 财政年份:2010
- 资助金额:
$ 3.2万 - 项目类别:
Architecture and communication controlling the efficient generation of beta cells
控制β细胞有效生成的架构和通信
- 批准号:
8143507 - 财政年份:2010
- 资助金额:
$ 3.2万 - 项目类别:
Architecture and communication controlling the efficient generation of beta cells
控制β细胞有效生成的架构和通信
- 批准号:
8522280 - 财政年份:2010
- 资助金额:
$ 3.2万 - 项目类别:
Architecture and communication controlling the efficient generation of beta cells
控制β细胞有效生成的架构和通信
- 批准号:
8717653 - 财政年份:2010
- 资助金额:
$ 3.2万 - 项目类别:
Architecture and communication controlling the efficient generation of beta cells
控制β细胞有效生成的架构和通信
- 批准号:
7994960 - 财政年份:2010
- 资助金额:
$ 3.2万 - 项目类别:
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