Expression of the mouse Fgf15 gene is directly initiated by Sonic hedgehog signaling in the diencephalon and midbrain
Article first published online: 21 DEC 2004
Copyright © 2004 Wiley-Liss, Inc.
Volume 232, Issue 2, pages 282–292, February 2005
How to Cite
Saitsu, H., Komada, M., Suzuki, M., Nakayama, R., Motoyama, J., Shiota, K. and Ishibashi, M. (2005), Expression of the mouse Fgf15 gene is directly initiated by Sonic hedgehog signaling in the diencephalon and midbrain. Dev. Dyn., 232: 282–292. doi: 10.1002/dvdy.20236
- Issue published online: 13 JAN 2005
- Article first published online: 21 DEC 2004
- Manuscript Revised: 30 AUG 2004
- Manuscript Accepted: 30 AUG 2004
- Manuscript Received: 1 APR 2004
- The Japanese Ministry of Health, Labor, and Welfare. Grant Number: 14A-4
- The Japanese Ministry of Education, Culture, Sports Science, and Technology. Grant Numbers: 13470003, 15689004, 15016061, 16015264, 15066201
- Kato Memorial Bioscience Foundation
- Sonic hedgehog;
Sonic hedgehog (Shh) is a secreted molecule that is thought to regulate tissue growth and patterning in vertebrate embryos. Although it has been reported that Gli transcription factors mediate Shh signaling to the nucleus, little is known about developmental target genes of Gli. In the previous genetic study, we showed that Shh is required for Fgf15 expression in the diencephalon and midbrain. Here, we examined whether Fgf15 is a direct target of Shh signaling through Gli. Shh was expressed in the midline cells and Fgf15 in the medial region of the diencephalon/midbrain by the seven-somite stage. The Fgf15 expression domain coincided with that of Gli1 and overlapped with that of Gli2 at this stage. Fgf15 expression in the diencephalon/midbrain was greatly reduced in the seven-somite Shh mutant embryos. Transgenic analysis showed that the 3.6-kb 5′-flanking region of the Fgf15 gene is sufficient for induction of Fgf15 in the medial/ventral diencephalon/midbrain. Luciferase assay showed that the 3.6-kb Fgf15 enhancer/promoter was activated by Gli2. A Gli-binding site was located 1 kb upstream of the transcription start site and was required for expression in the medial/ventral diencephalon/midbrain in transgenic embryos and for activation in luciferase assay. These findings indicate that Fgf15 is directly regulated by Shh signaling through Gli proteins. Developmental Dynamics 232:282–292, 2005. © 2004 Wiley-Liss, Inc.