Periodic Lunatic fringe expression is controlled during segmentation by a cyclic transcriptional enhancer responsive to notch signaling.
A molecular oscillator regulates the pace of vertebrate segmentation. Here, we show that the oscillator (clock) controls cyclic initiation of transcription in the unsegmented presomitic mesoderm (PSM). We identify an evolutionarily conserved 2.3 kb region in the murine Lunatic fringe (Lfng) promoter that drives periodic expression in the PSM. This region includes conserved blocks required for enhancing and repressing cyclic Lfng transcription, and to prevent continued expression in formed somites. We also show that dynamic expression in the cycling PSM is lost in the total absence of Notch signaling, and that Notch signaling acts directly via CBF1/RBP-Jkappa binding sites to regulate Lfng. These results are consistent with a model in which oscillatory Notch signaling underlies the segmentation clock and directly activates and indirectly represses Lfng expression.
Developmental Genetics Laboratory, Cancer Research UK, 44 Lincoln's Inn Field, London WC2A 3PX, United Kingdom.
Aixa V
AV
Morales
Yuko
Y
Yasuda
David
D
Ish-Horowicz
D000818:Animals; D030161:Avian Proteins; D001683:Biological Clocks / Q000235:genetics*; D019521:Body Patterning / Q000235:genetics*; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D016695:Glycosyltransferases / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010507:Periodicity; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D051880:Receptors, Notch; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000502:physiology; D015533:Transcriptional Activation / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D030161:Avian Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D051880:Receptors, Notch; D016695:Glycosyltransferases; C498394:LFNG protein, Gallus gallus; C498392:Lfng protein, mouse; D001616:beta-Galactosidase