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

Dev Dyn. 2012 Mar;241(3):493-504. doi: 10.1002/dvdy.23739. Epub 2012 Jan 25.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 2 / genetics
  • Animals
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Gene Deletion
  • Heart Defects, Congenital / genetics
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism*
  • Integrases / genetics
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Jagged-1 Protein
  • Lens, Crystalline / embryology*
  • Lens, Crystalline / metabolism
  • Liver / abnormalities
  • Liver / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Receptors, Notch / metabolism*
  • Serrate-Jagged Proteins
  • Signal Transduction

Substances

  • Adaptor Protein Complex 2
  • Calcium-Binding Proteins
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Intercellular Signaling Peptides and Proteins
  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Membrane Proteins
  • Rbpj protein, mouse
  • Receptors, Notch
  • Serrate-Jagged Proteins
  • Cre recombinase
  • Integrases