Fungiform papilla pattern: EGF regulates inter-papilla lingual epithelium and decreases papilla number by means of PI3K/Akt, MEK/ERK, and p38 MAPK signaling.
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.
Liu
Hong-Xiang
HX
Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, USA.
Henson
Bradley S
BS
Zhou
Yanqiu
Y
D'Silva
Nisha J
NJ
Mistretta
Charlotte M
CM
D000818:Animals; D015153:Blotting, Western; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D004848:Epithelium / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013650:Taste Buds / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D014059:Tongue / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure
D011518:Proto-Oncogene Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases