Platelet-derived growth factor receptor regulates salivary gland morphogenesis via fibroblast growth factor expression

Shinya Yamamoto, Emiko Fukumoto, Keigo Yoshizaki, Tsutomu Iwamoto, Aya Yamada, Kojiro Tanaka, Hiroharu Suzuki, Shizuko Aizawa, Makiko Arakaki, Kenji Yuasa, Kyoko Oka, Yang Chai, Kazuaki Nonaka, Satoshi Fukumoto

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41 Citations (Scopus)

Abstract

A coordinated reciprocal interaction between epithelium and mesenchyme is involved in salivary gland morphogenesis. The submandibular glands (SMGs) of Wnt1-Cre/R26R mice have been shown positive for mesenchyme, whereas the epithelium is β-galactosidase-negative, indicating that most mesenchymal cells are derived from cranial neural crest cells. Platelet-derived growth factor (PDGF) receptor α is one of the markers of neural crest-derived cells. In this study, we analyzed the roles of PDGFs and their receptors in the morphogenesis of mouse SMGs. PDGF-A was shown to be expressed in SMG epithelium, whereas PDGF-B, PDGFRα, and PDGFRβ were expressed in mesenchyme. Exogenous PDGF-AA and -BB in SMG organ cultures demonstrated increased levels of branching and epithelial proliferation, although their receptors were found to be expressed in mesenchyme. In contrast, short interfering RNA for Pdgfa and -b as well as neutralizing antibodies for PDGF-AB and -BB showed decreased branching. PDGF-AA induced the expression of the fibroblast growth factor genes Fgf3 and -7, and PDGF-BB induced the expression of Fgf1, -3, -7, and -10, whereas short interfering RNA for Pdgfa and Pdgfb inhibited the expression of Fgf3, -7, and -10, indicating that PDGFs regulate Fgf gene expression in SMG mesenchyme. The PDGF receptor inhibitor AG-17 inhibited PDGF-induced branching, whereas exogenous FGF7 and -10 fully recovered. Together, these results indicate that fibroblast growth factors function downstream of PDGF signaling, which regulates Fgf expression in neural crest-derived mesenchymal cells and SMG branching morphogenesis. Thus, PDGF signaling is a possible mechanism involved in the interaction between epithelial and neural crest-derived mesenchyme.

Original languageEnglish
Pages (from-to)23139-23149
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number34
DOIs
Publication statusPublished - Aug 22 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yamamoto, S., Fukumoto, E., Yoshizaki, K., Iwamoto, T., Yamada, A., Tanaka, K., Suzuki, H., Aizawa, S., Arakaki, M., Yuasa, K., Oka, K., Chai, Y., Nonaka, K., & Fukumoto, S. (2008). Platelet-derived growth factor receptor regulates salivary gland morphogenesis via fibroblast growth factor expression. Journal of Biological Chemistry, 283(34), 23139-23149. https://doi.org/10.1074/jbc.M710308200