Mouse Serrate-1 (Jagged-1): expression in the developing tooth is regulated by epithelial-mesenchymal interactions and fibroblast growth factor-4.
Serrate-like genes encode transmembrane ligands to Notch receptors and control cell fate decisions during development. In this report, we analyse the regulation of the mouse Serrate-1 gene during embryogenesis. The Serrate-1 gene is expressed from embryonic day 7.5 (E7.5) and expression is often observed at sites of epithelial-mesenchymal interactions, including the developing tooth, where Serrate-1 is first (E11.5) expressed in all cells of the dental epithelium, but not in mesenchyme. A transient upregulation in dental mesenchyme (E12.5-15.5) is correlated with down-regulation of Serrate-1 expression in epithelial cells contacting the mesenchyme, i.e. in the cells destined to become ameloblasts. This expression pattern is reproduced in explants of dental epithelium and mesenchyme in vitro: epithelium induces Serrate-1 expression in mesenchyme, while epithelium in close proximity to this mesenchyme does not express detectable levels of Serrate-1 mRNA, suggesting that down-regulation of Serrate-1 expression in preameloblasts is caused by mesenchyme-derived signals. Finally, regulation of Serrate-1 expression differs from that of Notch genes. The Serrate-1 gene is induced in dental mesenchyme by fibroblast growth factor-4, but not by bone morphogenetic proteins, while the converse is true for Notch genes. This indicates that, at least during tooth development, the expression patterns observed for receptors and ligands in the Notch signaling pathway are generated by different induction mechanisms.
Mitsiadis
T A
TA
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden. mitsiadi@ibdm.uviv-mrs.fr
Henrique
D
D
Thesleff
I
I
Lendahl
U
U
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002135:Calcium-Binding Proteins; D002455:Cell Division; D003001:Cloning, Molecular; D004627:Embryonic Induction; D004848:Epithelium / Q000502:physiology; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014018:Tissue Distribution; D014070:Tooth / Q000196:embryology*
D019485:Bone Morphogenetic Proteins; D002135:Calcium-Binding Proteins; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D005346:Fibroblast Growth Factors