Overexpression of Smad2 in Tgf-β3-null mutant mice rescues cleft palate

Xiao Mei Cui, Nobuyuki Shiomi, Jucheng Chen, Takashi Saito, Tadashi Yamamoto, Yoshihiro Ito, Pablo Bringas, Yang Chai, Charles F. Shuler

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Abstract

Transforming growth factor (TGF)-β3 is an important contributor to the regulation of medial edge epithelium (MEE) disappearance during palatal fusion. SMAD2 phosphorylation in the MEE has been shown to be directly regulated by TGF-β3. No phospho-SMAD2 was identified in the MEE in Tgf-β3-null mutant mice (Tgf-β3 -/- ), which was correlated with the persistence of the MEE and failure of palatal fusion. In the present study, the cleft palate phenotype in Tgf-β3 -/- mice was rescued by overexpression of a Smad2 transgene in Keratin 14-synthesizing MEE cells following mating Tgf-β3 heterozygous mice with Keratin 14 promoter directed Smad2 transgenic mice (K14-Smad2). Success of the rescue could be attributed to the elevated phospho-SMAD2 level in the MEE, demonstrated by two indirect evidences. The rescued palatal fusion in Tgf-β3 -/- /K14-Smad2 mice, however, never proceeded to the junction of primary and secondary palates and the most posterior border of the soft palate, despite phospho-SMAD2 expression in these regions at the same level as in the middle portion of the secondary palate. The K14-Smad2 transgene was unable to restore all the functional outcomes of TGF-β3. This may indicate an anterior-posterior patterning in the palatal shelves with respect to TGF-β3 signaling and the mechanism of secondary palatal fusion.

Original languageEnglish
Pages (from-to)193-202
Number of pages10
JournalDevelopmental Biology
Volume278
Issue number1
DOIs
Publication statusPublished - Feb 1 2005
Externally publishedYes

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Keywords

  • Cleft palate
  • Epithelial-mesenchymal transformation
  • Keratin 14
  • Medial edge epithelium
  • Mouse
  • Overexpression
  • Palatal fusion
  • Rescue
  • Smad2
  • TGF-β3

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Cui, X. M., Shiomi, N., Chen, J., Saito, T., Yamamoto, T., Ito, Y., Bringas, P., Chai, Y., & Shuler, C. F. (2005). Overexpression of Smad2 in Tgf-β3-null mutant mice rescues cleft palate. Developmental Biology, 278(1), 193-202. https://doi.org/10.1016/j.ydbio.2004.10.023