MOUSE SERRATE-1 (JAGGED-1) - EXPRESSION IN THE DEVELOPING TOOTH IS REGULATED BY EPITHELIAL-MESENCHYMAL INTERACTIONS AND FIBROBLAST GROWTH FACTOR-IV

Serrate-like genes encode transmembrane ligands to Notch receptors and control cell fate decisions during development. In this report, we an alyse the regulation of the mouse Serrate-1 gene during embryogenesis. The Serrate-1 gene is expressed from embryonic day 7.5 (E7.5) and exp ression is often observed at sites of epithelial-mesenchymal interacti ons, 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 correl ated with down-regulation of Serrate-1 expression in epithelial cells contacting the mesenchyme, i.e. in the cells destined to become amelob lasts. This expression pattern is reproduced in explants of dental epi thelium and mesenchyme in vitro: epithelium induces Serrate-1 expressi on in mesenchyme, while epithelium in close proximity to this mesenchy me does not express detectable levels of Serrate-1 mRNA, suggesting th at down-regulation of Serrate-1 expression in preameloblasts is caused by mesenchyme-derived signals. Finally, regulation of Serrate-1 expre ssion differs from that of Notch genes. The Serrate-1 gene is induced in dental mesenchyme by fibroblast growth factor-4, but not by bone mo rphogenetic proteins, while the converse is true for Notch genes. This indicates that, at least during tooth development, the expression pat terns observed for receptors and ligands in the Notch signaling pathwa y are generated by different induction mechanisms.