title: The atypical mammalian ligand Delta-like homologue 1 (Dlk1) can regulate Notch signalling in Drosophila.
abstract: BACKGROUND
  Mammalian Delta-like 1 (Dlk-1) protein shares homology with Notch ligands but lacks a critical receptor-binding domain. Thus it is unclear whether it is able to interact with Notch in vivo. Unlike mammals, Drosophila have a single Notch receptor allowing a simple in vivo assay for mammalian Dlk1 function.
  
  
  RESULTS
  Here we show that membrane-bound DLK1 can regulate Notch leading to altered cellular distribution of Notch itself and inhibiting expression of Notch target genes. The resulting adult phenotypes are indicative of reduced Notch function and are enhanced by Notch mutations, confirming that DLK1 action is antagonistic. In addition, cells expressing an alternative Dlk1 isoform exhibit alterations in cell size, functions previously not attributed to Notch suggesting that DLK1 might also act via an alternative target.
  
  
  CONCLUSIONS
  Our results demonstrate that DLK1 can regulate the Notch receptor despite its atypical structure.
authors.affiliation: Department of Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK. sjb32@cam.ac.uk
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Bray
authors.forename: Shuji
authors.initials: S
authors.lastname: Takada
authors.forename: Emma
authors.initials: E
authors.lastname: Harrison
authors.forename: Shing-Chuan
authors.initials: SC
authors.lastname: Shen
authors.forename: Anne C
authors.initials: AC
authors.lastname: Ferguson-Smith
mesh_terms: D000818:Animals; D002452:Cell Count; D004331:Drosophila melanogaster / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D051880:Receptors, Notch / Q000378:metabolism*; D012679:Sense Organs / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D020033:Protein Isoforms; D051880:Receptors, Notch