Removal of stem cell factor or addition of monoclonal anti-c-KIT antibody induces apoptosis in murine melanocyte precursors

Masaru Ito, Yoko Kawa, Hirotake Ono, Mitsuhiro Okura, Takako Baba, Yasuo Kubota, Sin Ichi Nishikawa, Masako Mizoguchi

Research output: Contribution to journalArticle

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Abstract

Previous findings indicate that the protein c-KIT and its ligand, stem cell factor (SCF) play a crucial role in the development of melanocytes from their precursors in the embryonic neural crest cells. Using a monoclonal anti-c-KIT antibody, ACK2, which is an antagonistic blocker of c-KIT function, we and others demonstrated that mouse melanocytes disappeared with the injection of ACK2 during certain periods of embryonic and postnatal life. The precise mechanisms of this disappearance, however, remain unclear. Because melanocytes disappeared without any inflammation in these in vivo studies, we suspect that apoptosis was a main cause of their disappearance. In this study, to clarify the underlying mechanism, we studied whether ACK2 induces apoptosis in c-KIT-positive melanoblasts, which appear in mouse neural crest cells cultured with SCF from 9.5 d old mouse embryos. With an in situ apoptosis detection kit, a significant increase in apoptosis was detected after the removal of SCF, which further increased with the addition of ACK2 during SCF-dependent periods. The occurrence of apoptosis in the cultured cells was also demonstrated by a DNA analysis and electron microscopy. Immunohistochemical double staining confirmed that the apoptotic cells were c-KIT positive, and the electron microscopy showed that these apoptotic cells were melanocyte precursors. It was therefore demonstrated that apoptosis was induced in the SCF-dependent c-KIT-positive melanocytes in vitro when the SCF/c-KIT interaction was obstructed. These findings elucidate the mechanism of the regulation of melanocyte development, and the survival and proliferation of these precursor cells, by SCF/c-KIT interaction.

Original languageEnglish
Pages (from-to)796-801
Number of pages6
JournalJournal of Investigative Dermatology
Volume112
Issue number5
DOIs
Publication statusPublished - 1999

Fingerprint

Stem Cell Factor
Melanocytes
Apoptosis
Neural Crest
Cells
Electron microscopy
Electron Microscopy
anti-c antibody
Cultured Cells
Embryonic Structures
Cell Proliferation
Staining and Labeling
Ligands
Inflammation
Injections
DNA

Keywords

  • c-KIT receptor
  • Melanoblast
  • Neural crest cell
  • Premelanosome

ASJC Scopus subject areas

  • Dermatology

Cite this

Removal of stem cell factor or addition of monoclonal anti-c-KIT antibody induces apoptosis in murine melanocyte precursors. / Ito, Masaru; Kawa, Yoko; Ono, Hirotake; Okura, Mitsuhiro; Baba, Takako; Kubota, Yasuo; Nishikawa, Sin Ichi; Mizoguchi, Masako.

In: Journal of Investigative Dermatology, Vol. 112, No. 5, 1999, p. 796-801.

Research output: Contribution to journalArticle

Ito, Masaru ; Kawa, Yoko ; Ono, Hirotake ; Okura, Mitsuhiro ; Baba, Takako ; Kubota, Yasuo ; Nishikawa, Sin Ichi ; Mizoguchi, Masako. / Removal of stem cell factor or addition of monoclonal anti-c-KIT antibody induces apoptosis in murine melanocyte precursors. In: Journal of Investigative Dermatology. 1999 ; Vol. 112, No. 5. pp. 796-801.
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AU - Baba, Takako

AU - Kubota, Yasuo

AU - Nishikawa, Sin Ichi

AU - Mizoguchi, Masako

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