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

Authors

  • Tien T. Le,

    1. Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio
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  • Kevin W. Conley,

    1. Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio
    Current affiliation:
    1. Museum of Science and Industry, Chicago, IL 60637
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  • Timothy J. Mead,

    1. The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio
    Current affiliation:
    1. Department of Cell Biology, Cleveland Clinic Lerner Research Institute Cleveland, OH 44195
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  • Sheldon Rowan,

    1. Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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  • Katherine E. Yutzey,

    1. The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio
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  • Nadean L. Brown

    Corresponding author
    1. Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio
    • Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, ML 7007, 3333 Burnet Avenue, Cincinnati, OH, 45229
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Abstract

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 AP2α-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, AP2α-Cre-mediated deletion of Rbpj resulted in embryos with cardiac outflow tract and liver deformities, and perinatal lethality. Developmental Dynamics 241:493–504, 2012. © 2012 Wiley Periodicals, Inc.

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