The WNT/MYB pathway suppresses KIT expression to control the timing of salivary proacinar differentiation and duct formation

Shinji Matsumoto, Takayuki Kurimoto, M. Mark Taketo, Shinsuke Fujii, Akira Kikuchi

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Growth factor signaling is involved in the development of various organs, but how signaling regulates organ morphogenesis and differentiation in a coordinated manner remains to be clarified. Here, we show how WNT signaling controls epithelial morphogenetic changes and differentiation using the salivary gland as a model. Experiments using genetically manipulated mice and organ cultures revealed that WNT signaling at an early stage (E12-E15) of submandibular salivary gland (SMG) development inhibits end bud morphogenesis and differentiation into proacini by suppressing Kit expression through the upregulation of the transcription factor MYB, and concomitantly increasing the expression of distal progenitor markers. In addition, WNT signaling at the early stage of SMG development promoted end bud cell proliferation, leading to duct formation. WNT signaling reduction at a late stage (E16-E18) of SMG development promoted end bud maturation and suppressed duct formation. Thus, WNT signaling controls the timing of SMG organogenesis by keeping end bud cells in an undifferentiated bipotent state.

Original languageEnglish
Pages (from-to)2311-2324
Number of pages14
JournalDevelopment (Cambridge)
Volume143
Issue number13
DOIs
Publication statusPublished - Jul 1 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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