Periodic notch inhibition by lunatic fringe underlies the chick segmentation clock

Nature. 2003 Jan 16;421(6920):275-8. doi: 10.1038/nature01244. Epub 2003 Jan 12.


The segmented aspect of the vertebrate body plan first arises through the sequential formation of somites. The periodicity of somitogenesis is thought to be regulated by a molecular oscillator, the segmentation clock, which functions in presomitic mesoderm cells. This oscillator controls the periodic expression of 'cyclic genes', which are all related to the Notch pathway. The mechanism underlying this oscillator is not understood. Here we show that the protein product of the cyclic gene lunatic fringe (Lfng), which encodes a glycosyltransferase that can modify Notch activity, oscillates in the chick presomitic mesoderm. Overexpressing Lfng in the paraxial mesoderm abolishes the expression of cyclic genes including endogenous Lfng and leads to defects in segmentation. This effect on cyclic genes phenocopies inhibition of Notch signalling in the presomitic mesoderm. We therefore propose that Lfng establishes a negative feedback loop that implements periodic inhibition of Notch, which in turn controls the rhythmic expression of cyclic genes in the chick presomitic mesoderm. This feedback loop provides a molecular basis for the oscillator underlying the avian segmentation clock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Proteins
  • Biological Clocks*
  • Body Patterning*
  • Chick Embryo
  • Feedback, Physiological
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Glycosyltransferases / genetics
  • Glycosyltransferases / metabolism*
  • In Situ Hybridization
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • Periodicity*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Notch
  • Somites / cytology
  • Somites / metabolism


  • Avian Proteins
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Notch
  • Glycosyltransferases
  • LFNG protein, Gallus gallus