ISLET1-dependent β-catenin/hedgehog signaling is required for outgrowth of the lower jaw

Feixue Li, Guoquan Fu, Ying Liu, Xiaoping Miao, Yan Li, Xueqin Yang, Xiaoyun Zhang, Dongliang Yu, Lin Gan, Mengsheng Qiu, Yiping Chen, Ze Zhang, Zunyi Zhang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Mandibular patterning information initially resides in the epithelium during development. However, how transcriptional regulation of epithelium-derived signaling controls morphogenesis of the mandible remains elusive. Using ShhCre to target the mandibular epithelium, we ablated transcription factor Islet1, resulting in a distally truncated mandible via unbalanced cell apoptosis and decreased cell proliferation in the distal mesenchyme. Loss of Islet1 caused a lack of cartilage at the distal tip, leading the fusion of two growing mandibular elements surrounding the rostral process of Meckel's cartilage. Loss of Islet1 results in dysregulation of mesenchymal genes important for morphogenesis of the mandibular arch. We revealed that Islet1 is required for the activation of epithelial β-catenin signaling via repression of Wnt antagonists. Reactivation of β-catenin in the epithelium of the Islet1 mutant rescued mandibular morphogenesis through sonic hedgehog (SHH) signaling to the mesenchyme. Furthermore, overexpression of a transgenic hedgehog ligand in the epithelium also partially restored outgrowth of the mandible. These data reveal functional roles for an ISLET1-dependent network integrating β-catenin/SHH signals in mesenchymal cell survival and outgrowth of the mandible during development.

Original languageEnglish (US)
Article numbere00590-16
JournalMolecular and Cellular Biology
Volume37
Issue number8
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Keywords

  • Epithelium
  • Islet1
  • Mandibular growth
  • Mesenchyme
  • SHH pathway
  • β-catenin signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Li, F., Fu, G., Liu, Y., Miao, X., Li, Y., Yang, X., Zhang, X., Yu, D., Gan, L., Qiu, M., Chen, Y., Zhang, Z., & Zhang, Z. (2017). ISLET1-dependent β-catenin/hedgehog signaling is required for outgrowth of the lower jaw. Molecular and Cellular Biology, 37(8), [e00590-16]. https://doi.org/10.1128/MCB.00590-16