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The interactions of TGF-beta signalling pathway and Jagged2/Notch1 pathway induce acanthosis in lingual epithelia

Feng Li1, Mingliang Zhou

  • 11Department of Laboratory Animal Science, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China 2Monell Chemical Senses Center, Philadelphia, PA, United States.

Pathology
|September 10, 2014
PubMed

Insights

TGF-β signaling disruption impacts tongue development, initially inhibiting filiform papillae but later causing epithelial proliferation. These effects involve complex interactions with the Jagged2/Notch1 pathway and epigenetic modifications.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Stem Cell Biology

Background:

  • Transforming growth factor-beta (TGF-β) signaling is crucial for epithelial development.
  • The role of TGF-β in tongue epithelial stem cell regulation and its interplay with other pathways remain incompletely understood.

Purpose of the Study:

  • To differentiate primary and secondary effects of TGF-β signaling disruption in NTPDase2+ cells.
  • To explore interactions between TGF-β signaling and the Jagged2/Notch1 pathway in regulating tongue epithelial stem cell expansion.

Main Methods:

  • Utilized inducible dominant-negative TGF-β receptor type II (Tgfbr2) mutant mice.
  • Employed doxycycline (Dox) treatment to control Tgfbr2 disruption in specific cell populations (NTPDase2+ or K14 promoter-driven).
  • Analyzed effects on filiform papillae formation and lingual epithelial proliferation in different tongue regions.

Main Results:

  • TGF-β signaling disruption initially inhibited filiform papillae but led to their regeneration.
  • Induced lingual epithelial proliferation in the middle and posterior tongue regions.
  • Identified interactions between TGF-β, Jagged2/Notch1 pathways, and epigenetic modifications in stem cell expansion.

Conclusions:

  • Distinct molecular mechanisms regulate lingual epithelia and filiform papillae development based on location.
  • TGF-β signaling, Jagged2/Notch1 pathway, and epigenetic modifications collectively regulate lingual epithelial stem cell expansion.
  • Observed fluctuating tongue epithelial phenotypes suggest combined signaling and epigenetic influences over time.

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