title: Multipotency of melanoblasts isolated from murine skin depends on the Notch signal.
abstract: BACKGROUND
  Melanoblasts (MBs), derived from neural crest cells, only differentiate into melanocytes (Ms) in vivo. We previously showed that MBs isolated from mouse skin were multipotent, generating neurons (Ns) and glial cells (Gs) together with Ms. Using Sox10-IRES-Venus mice and mouse embryonic stem cells, we investigated how MBs expressed their multipotency.
  
  
  RESULTS
  MBs generated colonies containing Ns, Gs, and Ms in the presence of ST2 stromal cells, but they generated only M colonies when incubated with keratinocytes or ST2 culture supernatant, thus showing that MBs required contact with ST2 stromal cells for expression of their multipotency. Notch signaling was shown to be one of the important cues for the maintenance and differentiation of MBs through cell-cell contact. When Notch signaling was inhibited, MBs mainly generated colonies that contained just one type of cells, Ns, Gs, or Ms; the number of colonies containing two or three types of cells markedly decreased even on ST2 stromal cells, showing restriction of their differentiation potency. Whereas when Notch signaling was activated, the number of colonies containing two or three types of cells increased, indicating that their multipotency had been maintained.
  
  
  CONCLUSIONS
  Our results demonstrate that Notch signaling played novel roles in MB multipotency.
authors.affiliation: Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Motohashi
authors.affiliation: Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishioka
authors.affiliation: Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Norito
authors.initials: N
authors.lastname: Kawamura
authors.affiliation: Fukushima Project Headquarters, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hirobe
authors.affiliation: Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kunisada
mesh_terms: D000818:Animals; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000378:metabolism*
chemical_list: D051880:Receptors, Notch
keywords: ES cells; Kit; Sox10; cell-cell contact; mouse embryo