Priming, initiation and synchronization of the segmentation clock by deltaD and deltaC

Nat Cell Biol. 2007 May;9(5):523-30. doi: 10.1038/ncb1578. Epub 2007 Apr 8.


Zebrafish somitogenesis is governed by a segmentation clock that generates oscillations in expression of several Notch pathway genes, including her1, her7 and deltaC. Using a combination of pharmacological inhibition and Mendelian genetics, we show that DeltaD and DeltaC, two Notch ligands, represent functionally distinct signals within the segmentation clock. Using high-resolution fluorescent in situ hybridization, the oscillations were divided into phases based on eight distinct subcellular patterns of mRNA localization for 140,000 cells. her1, her7 and deltaC expression was examined in wild-type, deltaD(-/-) and deltaC(-/-) embryos. We identified areas within the tailbud where the clock is set up in the progenitor cells (priming), where the clock starts running (initiation), and where the clocks of neighbouring cells are entrained (synchronization). We find that the clocks of motile cells are primed by deltaD in a progenitor zone in the posterior tailbud and that deltaD is required for cells to initiate oscillations on exiting this zone. Oscillations of adjacent cells are synchronized and amplified by deltaC in the posterior presomitic mesoderm as cell movement subsides and cells maintain stable neighbour relationships.

Publication types

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

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biological Clocks* / drug effects
  • Cell Movement
  • Dipeptides / pharmacology
  • Embryonic Stem Cells / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Developmental* / drug effects
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microinjections
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Notch / metabolism
  • Signal Transduction
  • Somites / drug effects
  • Somites / metabolism*
  • Time Factors
  • Tissue Culture Techniques
  • Transcription Factors / metabolism
  • Zebrafish / embryology*
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • Basic Helix-Loop-Helix Transcription Factors
  • Dipeptides
  • Enzyme Inhibitors
  • HER7 protein, zebrafish
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, Notch
  • Transcription Factors
  • Zebrafish Proteins
  • delta protein
  • dld protein, zebrafish
  • her1 protein, zebrafish
  • Amyloid Precursor Protein Secretases