Divergent functions and distinct localization of the Notch ligands DLL1 and DLL3 in vivo

J Cell Biol. 2007 Jul 30;178(3):465-76. doi: 10.1083/jcb.200702009.

Abstract

The Notch ligands Dll1 and Dll3 are coexpressed in the presomitic mesoderm of mouse embryos. Despite their coexpression, mutations in Dll1 and Dll3 cause strikingly different defects. To determine if there is any functional equivalence, we replaced Dll1 with Dll3 in mice. Dll3 does not compensate for Dll1; DLL1 activates Notch in Drosophila wing discs, but DLL3 does not. We do not observe evidence for antagonism between DLL1 and DLL3, or repression of Notch activity in mice or Drosophila. In vitro analyses show that differences in various domains of DLL1 and DLL3 individually contribute to their biochemical nonequivalence. In contrast to endogenous DLL1 located on the surface of presomitic mesoderm cells, we find endogenous DLL3 predominantly in the Golgi apparatus. Our data demonstrate distinct in vivo functions for DLL1 and DLL3. They suggest that DLL3 does not antagonize DLL1 in the presomitic mesoderm and warrant further analyses of potential physiological functions of DLL3 in the Golgi network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Body Patterning
  • Calcium-Binding Proteins
  • Cell Line
  • Drosophila melanogaster / anatomy & histology
  • Drosophila melanogaster / embryology
  • Embryo, Mammalian / anatomy & histology
  • Embryo, Mammalian / metabolism*
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Ligands
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Phenotype
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Protein Structure, Tertiary
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology*
  • Somites / anatomy & histology
  • Somites / physiology
  • Tissue Distribution
  • Wings, Animal / anatomy & histology
  • Wings, Animal / embryology

Substances

  • Calcium-Binding Proteins
  • Dlk1 protein, mouse
  • Dll3 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins
  • Protein Isoforms
  • Receptors, Notch
  • Recombinant Fusion Proteins