title: The WNT/MYB pathway suppresses KIT expression to control the timing of salivary proacinar differentiation and duct formation.
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.
authors.affiliation: Departments of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Departments of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan The First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kurimoto
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo, Kyoto 606-8501, Japan.
authors.forename: M Mark
authors.initials: MM
authors.lastname: Taketo
authors.affiliation: Departments of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Departments of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan akikuchi@molbiobc.med.osaka-u.ac.jp.
authors.forename: Akira
authors.identifier: 0000-0003-3378-9522
authors.initials: A
authors.lastname: Kikuchi
mesh_terms: D061354:Acinar Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D013363:Submandibular Gland / Q000166:cytology* / Q000187:drug effects / Q000196:embryology*; D013997:Time Factors; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D020598:Proto-Oncogene Proteins c-myb; D005346:Fibroblast Growth Factors; D019869:Phosphatidylinositol 3-Kinases; D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt
keywords: Differentiation; KIT; MYB; Morphogenesis; Mouse; Salivary gland; WNT