Clock regulatory elements control cyclic expression of Lunatic fringe during somitogenesis.
Somitogenesis requires a segmentation clock and Notch signaling. Lunatic fringe (Lfng) expression in the presomitic mesoderm (PSM) cycles in the posterior PSM, is refined in the segmenting somite to the rostral compartment, and is required for segmentation. We identify distinct cis-acting regulatory elements for each aspect of Lfng expression. Fringe clock element 1 (FCE1) represents a conserved 110 bp region that is necessary to direct cyclic Lfng RNA expression in the posterior PSM. Mutational analysis of E boxes within FCE1 indicates a potential interplay of positive and negative transcriptional regulation by cyclically expressed bHLH proteins. A separable Lfng regulatory region directs expression to the prospective rostral aspect of the condensing somite. These independent Lfng regulatory cassettes advance a molecular framework for deciphering somite segmentation.
Cole
Susan E
SE
Department of Molecular Biology and Howard Hughes Medical Institute, Princeton University, Princeton, NJ 08544, USA.
Levorse
John M
JM
Tilghman
Shirley M
SM
Vogt
Thomas F
TF
D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks / Q000235:genetics*; D019521:Body Patterning / Q000235:genetics*; D004252:DNA Mutational Analysis; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005809:Genes, Regulator / Q000235:genetics*; D016695:Glycosyltransferases / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007763:Lac Operon / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011247:Pregnancy; D017434:Protein Structure, Tertiary / Q000235:genetics; D012313:RNA / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D019170:Somites / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D016695:Glycosyltransferases; D018398:Homeodomain Proteins; D012313:RNA; D014157:Transcription Factors; C489816:Hoxc8 protein, mouse; C107407:Mesp2 protein, mouse; C498392:Lfng protein, mouse