Apc inhibition of Wnt signaling regulates supernumerary tooth formation during embryogenesis and throughout adulthood.
The ablation of Apc function or the constitutive activation of beta-catenin in embryonic mouse oral epithelium results in supernumerary tooth formation, but the underlying mechanisms and whether adult tissues retain this potential are unknown. Here we show that supernumerary teeth can form from multiple regions of the jaw and that they are properly mineralized, vascularized, innervated and can start to form roots. Even adult dental tissues can form new teeth in response to either epithelial Apc loss-of-function or beta-catenin activation, and the effect of Apc deficiency is mediated by beta-catenin. The formation of supernumerary teeth via Apc loss-of-function is non-cell-autonomous. A small number of Apc-deficient cells is sufficient to induce surrounding wild-type epithelial and mesenchymal cells to participate in the formation of new teeth. Strikingly, Msx1, which is necessary for endogenous tooth development, is dispensable for supernumerary tooth formation. In addition, we identify Fgf8, a known tooth initiation marker, as a direct target of Wnt/beta-catenin signaling. These studies identify key mechanistic features responsible for supernumerary tooth formation.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Xiu-Ping
XP
Wang
Daniel J
DJ
O'Connell
Jennifer J
JJ
Lund
Irfan
I
Saadi
Mari
M
Kuraguchi
Annick
A
Turbe-Doan
Resy
R
Cavallesco
Hyunsoo
H
Kim
Peter J
PJ
Park
Hidemitsu
H
Harada
Raju
R
Kucherlapati
Richard L
RL
Maas
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D047108:Embryonic Development; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction; D014096:Tooth, Supernumerary / Q000196:embryology* / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein; C496457:Fgf8 protein, mouse; D051957:MSX1 Transcription Factor; C484084:Msx1 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin; D051524:Fibroblast Growth Factor 8