FGF signaling sustains the odontogenic fate of dental mesenchyme by suppressing β-catenin signaling.
Odontoblasts and osteoblasts develop from multipotent craniofacial neural crest cells during tooth and jawbone development, but the mechanisms that specify and sustain their respective fates remain largely unknown. In this study we used early mouse molar and incisor tooth germs that possess distinct tooth-forming capability after dissociation and reaggregation in vitro to investigate the mechanism that sustains odontogenic fate of dental mesenchyme during tooth development. We found that after dissociation and reaggregation, incisor, but not molar, mesenchyme exhibits a strong osteogenic potency associated with robustly elevated β-catenin signaling activity in a cell-autonomous manner, leading to failed tooth formation in the reaggregates. Application of FGF3 to incisor reaggregates inhibits β-catenin signaling activity and rescues tooth formation. The lack of FGF retention on the cell surface of incisor mesenchyme appears to account for the differential osteogenic potency between incisor and molar, which can be further attributed to the differential expression of syndecan 1 and NDST genes. We further demonstrate that FGF signaling inhibits intracellular β-catenin signaling by activating the PI3K/Akt pathway to regulate the subcellular localization of active GSK3β in dental mesenchymal cells. Our results reveal a novel function for FGF signaling in ensuring the proper fate of dental mesenchyme by regulating β-catenin signaling activity during tooth development.
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Chao
C
Liu
Shuping
S
Gu
Cheng
C
Sun
Wenduo
W
Ye
Zhongchen
Z
Song
Yanding
Y
Zhang
YiPing
Y
Chen
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D051518:Fibroblast Growth Factor 3 / Q000378:metabolism* / Q000494:pharmacology; D005697:Galactosides; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007211:Indoles; D008648:Mesoderm / Q000166:cytology / Q000196:embryology*; D051379:Mice; D008863:Microspheres; D009432:Neural Crest / Q000166:cytology; D009805:Odontogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014070:Tooth / Q000196:embryology*; D051176:beta Catenin / Q000378:metabolism
C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D005697:Galactosides; D007211:Indoles; D051176:beta Catenin; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside
FGF; Tooth development; β-catenin signaling