Requirements for Jag1-Rbpj mediated Notch signaling during early mouse lens development

被引:28
作者
Le, Tien T. [1 ]
Conley, Kevin W. [1 ]
Mead, Timothy J. [2 ]
Rowan, Sheldon [3 ,4 ]
Yutzey, Katherine E. [2 ]
Brown, Nadean L. [1 ]
机构
[1] Cincinnati Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH 45229 USA
[2] Cincinnati Childrens Hosp Res Fdn, Inst Heart, Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA
[3] Harvard Univ, Sch Med, Boston, MA USA
[4] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
关键词
lens development; lens fiber cells; cardiac outflow tract; liver development; Rbpj; Notch signaling; Jagged1; apoptosis; BILE-DUCT DEVELOPMENT; ALAGILLE-SYNDROME; TRANSCRIPTION FACTOR; HUMAN JAGGED1; MICE; DIFFERENTIATION; EXPRESSION; PATHWAY; EYE; GENE;
D O I
10.1002/dvdy.23739
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
Background: During vertebrate lens development, the lens placode in the embryonic ectoderm invaginates into a lens vesicle, which then separates from the surface epithelium, followed by two waves of fiber cell differentiation. In the mouse, multiple labs have shown that Jag1-Notch signaling is critically required during the second wave of lens fiber cell formation. However, Notch signaling appears to play no obvious role during lens induction or morphogenesis, although multiple pathway genes are expressed at these earlier stages. Results: Here, we explored functions for Notch signaling specifically during early lens development, by using the early-acting AP2a-Cre driver to delete Jag1 or Rbpj. We found that Jag1 and Rbpj are not required during lens induction, but are necessary for proper lens vesicle separation from the surface ectoderm. Conclusions: We conclude that precise levels of Notch signaling are essential during lens vesicle morphogenesis. In addition, AP2a-Cre-mediated deletion of Rbpj resulted in embryos with cardiac outflow tract and liver deformities, and perinatal lethality. Developmental Dynamics 241:493504, 2012. (c) 2012 Wiley Periodicals, Inc.
引用
收藏
页码:493 / 504
页数:12
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