Fungiform papilla pattern: EGF regulates inter-papilla lingual epithelium and decreases papilla number by means of PI3K/Akt, MEK/ERK, and p38 MAPK signaling
Article first published online: 26 AUG 2008
Copyright © 2008 Wiley-Liss, Inc.
Volume 237, Issue 9, pages 2378–2393, September 2008
How to Cite
Liu, H.-X., Henson, B. S., Zhou, Y., D'Silva, N. J. and Mistretta, C. M. (2008), Fungiform papilla pattern: EGF regulates inter-papilla lingual epithelium and decreases papilla number by means of PI3K/Akt, MEK/ERK, and p38 MAPK signaling. Dev. Dyn., 237: 2378–2393. doi: 10.1002/dvdy.21657
- Issue published online: 26 AUG 2008
- Article first published online: 26 AUG 2008
- Manuscript Accepted: 9 JUN 2008
- NIDCD, NIH. Grant Number: DC000456
- taste papilla;
- fungiform papilla;
- EGF/EGFR signaling;
- p38 MAP Kinase;
- tongue epithelium
Fungiform papillae are epithelial taste organs that form on the tongue, requiring differentiation of papillae and inter-papilla epithelium. We tested roles of epidermal growth factor (EGF) and the receptor EGFR in papilla development. Developmentally, EGF was localized within and between papillae whereas EGFR was progressively restricted to inter-papilla epithelium. In tongue cultures, EGF decreased papillae and increased cell proliferation in inter-papilla epithelium in a concentration-dependent manner, whereas EGFR inhibitor increased and fused papillae. EGF preincubation could over-ride disruption of Shh signaling that ordinarily would effect a doubling of fungiform papillae. With EGF-induced activation of EGFR, we demonstrated phosphorylation in PI3K/Akt, MEK/ERK, and p38 MAPK pathways; with pathway inhibitors (LY294002, U0126, SB203580) the EGF-mediated decrease in papillae was reversed, and synergistic actions were shown. Thus, EGF/EGFR signaling by means of PI3K/Akt, MEK/ERK, and p38 MAPK contributes to epithelial cell proliferation between papillae; this biases against papilla differentiation and reduces numbers of papillae. Developmental Dynamics 237:2378–2393, 2008. © 2008 Wiley-Liss, Inc.