A regulatory relationship between Tbx1 and FGF signaling during tooth morphogenesis and ameloblast lineage determination.
The Tbx1 gene is a transcriptional regulator involved in the DiGeorge syndrome, which affects normal facial and tooth development. Several clinical reports point to a common enamel defect in the teeth of patients with DiGeorge syndrome. Here, we have analyzed the expression, regulation, and function of Tbx1 during mouse molar development. Tbx1 expression is restricted to epithelial cells that give rise to the enamel producing ameloblasts and correlates with proliferative events. Tbx1 expression in epithelium requires mesenchyme-derived signals: dental mesenchyme induces expression of Tbx1 in recombined dental and non-dental epithelia. Bead implantation experiments show that FGF molecules are able to maintain epithelial Tbx1 expression during odontogenesis. Expression of Tbx1 in dental epithelium of FGF receptor 2b(-/-) mutant mice is downregulated, showing a genetic link between FGF signaling and Tbx1 in teeth. Forced expression of Tbx1 in dental explants activates amelogenin expression. These results indicate that Tbx1 expression in developing teeth is under control of FGF signaling and correlates with determination of the ameloblast lineage.
Department of Orofacial Development and Structure, Institute of Oral Biology, ZZMK, Faculty of Medicine, University of Zurich, Plattenstrasse 11, CH 8032 Zurich, Switzerland. thimios.mitsiadis@zzmk.uzh.ch
Thimios A
TA
Mitsiadis
Abigail S
AS
Tucker
Cosimo
C
De Bari
Martyn T
MT
Cobourne
David P C
DP
Rice
D000565:Ameloblasts / Q000166:cytology* / Q000187:drug effects; D053523:Amelogenin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018274:Electroporation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000196:embryology; D005346:Fibroblast Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000172:deficiency / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014070:Tooth / Q000166:cytology / Q000187:drug effects / Q000196:embryology*
D053523:Amelogenin; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; D005346:Fibroblast Growth Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2