Signaling by FGFR2b controls the regenerative capacity of adult mouse incisors

Sara Parsa, Koh Ichi Kuremoto, Kerstin Seidel, Reza Tabatabai, Bre Anne MacKenzie, Takayoshi Yamaza, Kentaro Akiyama, Jonathan Branch, Chester J. Koh, Denise Al Alam, Ophir D. Klein, Saverio Bellusci

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Rodent incisors regenerate throughout the lifetime of the animal owing to the presence of epithelial and mesenchymal stem cells in the proximal region of the tooth. Enamel, the hardest component of the tooth, is continuously deposited by stem cell-derived ameloblasts exclusively on the labial, or outer, surface of the tooth. The epithelial stem cells that are the ameloblast progenitors reside in structures called cervical loops at the base of the incisors. Previous studies have suggested that FGF10, acting mainly through fibroblast growth factor receptor 2b (FGFR2b), is crucial for development of the epithelial stem cell population in mouse incisors. To explore the role of FGFR2b signaling during development and adult life, we used an rtTA transactivator/tetracycline promoter approach that allows inducible and reversible attenuation of FGFR2b signaling. Downregulation of FGFR2b signaling during embryonic stages led to abnormal development of the labial cervical loop and of the inner enamel epithelial layer. In addition, postnatal attenuation of signaling resulted in impaired incisor growth, characterized by failure of enamel formation and degradation of the incisors. At a cellular level, these changes were accompanied by decreased proliferation of the transitamplifying cells that are progenitors of the ameloblasts. Upon release of the signaling blockade, the incisors resumed growth and reformed an enamel layer, demonstrating that survival of the stem cells was not compromised by transient postnatal attenuation of FGFR2b signaling. Taken together, our results demonstrate that FGFR2b signaling regulates both the establishment of the incisor stem cell niches in the embryo and the regenerative capacity of incisors in the adult.

Original languageEnglish
Pages (from-to)3743-3752
Number of pages10
JournalDevelopment
Volume137
Issue number22
DOIs
Publication statusPublished - Nov 15 2010

Keywords

  • Ameloblasts
  • Enamel
  • FGF10
  • Fibroblast growth factor receptor 2b
  • Incisor regeneration
  • Mouse
  • Stem cells

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Parsa, S., Kuremoto, K. I., Seidel, K., Tabatabai, R., MacKenzie, B. A., Yamaza, T., Akiyama, K., Branch, J., Koh, C. J., Al Alam, D., Klein, O. D., & Bellusci, S. (2010). Signaling by FGFR2b controls the regenerative capacity of adult mouse incisors. Development, 137(22), 3743-3752. https://doi.org/10.1242/dev.051672