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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
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Epithelial YAP1 Regulates Ameloblast Differentiation through SHH/FGF Signaling.

Y Zheng1, Y Qu1, H Liu1

  • 1Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, People's Republic of China.

Journal of Dental Research
|May 30, 2025
PubMed
Summary

Epithelial Yap1 (Yes-associated protein 1) is crucial for enamel formation by regulating ameloblast differentiation through the SHH/FGF signaling pathway. Its deletion impairs enamel development and tooth formation.

Keywords:
development biologyenamelepithelial-mesenchymal interactionsignal pathwaytoothtranscription factor

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Area of Science:

  • Dental Science
  • Developmental Biology
  • Molecular Biology

Background:

  • Enamel defects have significant clinical implications, impacting tooth sensitivity and mastication.
  • Yap1 (Yes-associated protein 1) is a transcriptional coactivator involved in cell proliferation and differentiation, with a known role in tooth development, but its precise mechanism in enamel formation is unclear.

Purpose of the Study:

  • To investigate the role of Yap1 in regulating enamel formation and ameloblast differentiation.
  • To elucidate the molecular mechanisms by which Yap1 influences these processes.

Main Methods:

  • Ablation of Yap1 in the dental epithelium of mice using Pitx2Cre.
  • Analysis of enamel formation, ameloblast differentiation markers (Amelx, Ambn, Mmp20), cell proliferation, and apoptosis in mutant incisors.
  • Transcriptome analysis and in situ hybridization to identify downstream signaling pathways.
  • In vitro and in vivo experiments to assess the interplay between SHH and FGF signaling.

Main Results:

  • Yap1 ablation in dental epithelium caused defective enamel formation and reduced expression of key ameloblast differentiation markers.
  • Cell proliferation was significantly reduced in Yap1-deficient incisors, without affecting apoptosis.
  • Yap1 deletion led to downregulation of SHH and FGF signaling pathway components.
  • SHH signaling was found to regulate FGF signaling, and Ihh (Indian hedgehog) overexpression could partially rescue Yap1 deletion phenotypes.

Conclusions:

  • Epithelial Yap1 plays a critical role in ameloblast differentiation and enamel formation.
  • Yap1 regulates enamel development by modulating the SHH/FGF signaling axis.
  • These findings provide insights into the molecular mechanisms underlying tooth development and potential therapeutic targets for enamel defects.