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YAP overexpression affects tooth morphogenesis and enamel knot patterning.

M Liu1, S Zhao, X P Wang

  • 1Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.

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|March 4, 2014
PubMed
Summary

Overexpressing YAP in developing teeth caused abnormal tooth shape and mislocated the enamel knot signaling center. This suggests the enamel knot may not be essential for initiating tooth signaling centers.

Keywords:
Hippo signalingdental laminaepithelial-mesenchymal interactionmorphogenesissignaling centertooth development

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Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Genetics

Background:

  • Tooth development involves precise morphological stages regulated by signaling centers.
  • The enamel knot is a transient structure in the enamel organ, crucial for tooth morphogenesis.
  • YAP, a Hippo pathway co-activator, regulates organ growth and development.

Purpose of the Study:

  • To investigate the role of YAP in tooth development.
  • To analyze the tooth phenotype in mice overexpressing active YAP in dental epithelium.
  • To understand the relationship between YAP, the enamel knot, and tooth signaling.

Main Methods:

  • Utilized transgenic mice overexpressing a constitutively active form of YAP in dental epithelium.
  • Analyzed tooth morphology and enamel knot characteristics.
  • Examined expression patterns of key signaling molecules (Shh, Fgf4, Wnt10a) and cellular markers (Edar, E-cadherin).

Main Results:

  • YAP overexpression led to deformed tooth morphogenesis and a widened dental lamina.
  • The enamel knot was mislocated, lacked proliferating cells, and contained apoptotic cells.
  • Key signaling molecules were not expressed in the mislocated enamel knot but remained at the enamel organ tip.

Conclusions:

  • YAP plays a critical role in regulating tooth morphogenesis and enamel knot formation.
  • Mislocation of the enamel knot suggests its induction might be independent of this structure.
  • Reciprocal epithelial-mesenchymal interactions are likely crucial for signaling center induction during tooth development.