A regulatory relationship between Tbx1 and FGF signaling during tooth morphogenesis and ameloblast lineage determination

Thimios A. Mitsiadis, Abigail S. Tucker, Cosimo De Bari, Martyn T. Cobourne, David P. C. Rice

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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(-1-) 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. (C) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalDevelopmental Biology
Volume320
Issue number1
Early online date16 Apr 2008
DOIs
Publication statusPublished - 1 Aug 2008

Keywords

  • T-box genes
  • Tbx1, FGF
  • transcription factors
  • cell fate
  • tooth
  • ameloblast
  • enamel
  • development
  • mouse
  • epithelial-mesenchymal interactions
  • fibroblast growth-factors
  • developing mouse tooth
  • ulnar-mammary syndrome
  • Holt-oram syndrome
  • cell-proliferation
  • digeorge-syndrome
  • retinoic acid

Cite this

A regulatory relationship between Tbx1 and FGF signaling during tooth morphogenesis and ameloblast lineage determination. / Mitsiadis, Thimios A.; Tucker, Abigail S.; De Bari, Cosimo; Cobourne, Martyn T.; Rice, David P. C.

In: Developmental Biology, Vol. 320, No. 1, 01.08.2008, p. 39-48.

Research output: Contribution to journalArticle

Mitsiadis, Thimios A. ; Tucker, Abigail S. ; De Bari, Cosimo ; Cobourne, Martyn T. ; Rice, David P. C. / A regulatory relationship between Tbx1 and FGF signaling during tooth morphogenesis and ameloblast lineage determination. In: Developmental Biology. 2008 ; Vol. 320, No. 1. pp. 39-48.
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N1 - Corrigendum to "A regulatory relationship between Tbx1 and FGF signaling during tooth morphogenesis and ameloblast lineage determination" [Dev. Biol. 320 (2008) 39-48] (DOI:10.1016/j.ydbio.2008.04.006) Thimios A. Mitsiadis, Abigail S. Tucker, Cosimo De Bari, Martyn T. Cobourne, David P.C. Rice, 2009, vol. 326, issue 2, p. 482. Developmental Biology

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N2 - 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(-1-) 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. (C) 2008 Elsevier Inc. All rights reserved.

AB - 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(-1-) 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. (C) 2008 Elsevier Inc. All rights reserved.

KW - T-box genes

KW - Tbx1, FGF

KW - transcription factors

KW - cell fate

KW - tooth

KW - ameloblast

KW - enamel

KW - development

KW - mouse

KW - epithelial-mesenchymal interactions

KW - fibroblast growth-factors

KW - developing mouse tooth

KW - ulnar-mammary syndrome

KW - Holt-oram syndrome

KW - cell-proliferation

KW - digeorge-syndrome

KW - retinoic acid

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SP - 39

EP - 48

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

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