Transcription factor expression and notch-dependent regulation of neural progenitors in the adult rat spinal cord

Shin Ichi Yamamoto, Motoshi Nagao, Michiya Sugimori, Hidetaka Kosako, Hirofumi Nakatomi, Naoya Yamamoto, Hirohide Takebayashi, Yo Ichi Nabeshima, Toshio Kitamura, Gerry Weinmaster, Kozo Nakamura, Masato Nakafuku

Research output: Contribution to journalArticle

206 Citations (Scopus)

Abstract

Recent studies have demonstrated that neural stem cells and other progenitors are present in the adult CNS. Details of their properties, however, remain poorly understood. Here we examined the properties and control mechanisms of neural progenitors in the adult rat spinal cord at the molecular level. Adult and embryonic progenitors commonly expressed various homeodomain-type (Pax6, Pax7, Nkx2.2, and Prox1) and basic helix-loop-helix (bHLH)-type (Ngn2, Mash1, NeuroD1, and Olig2) transcriptional regulatory factors in vitro. Unlike their embryonic counterparts, however, adult progenitors could not generate specific neurons that expressed markers appropriate for spinal motoneurons or interneurons, including Islet1, Lim1, Lim3, and HB9. Cells expressing the homeodomain factors Pax 6, Pax7, and Nkx2.2 also emerged in vivo in response to injury and were distributed in unique patterns in the lesioned spinal cord. However, neither the expression of the neurogenic bHLH factors including Ngn2, Mash1, and NeuroD1 nor subsequent generation of new neurons could be detected in injured tissue. Our results suggest that signaling through the cell-surface receptor Notch is involved in this restriction. The expression of Notch1 in vivo was enhanced in response to injury. Furthermore, activation of Notch signaling in vitro inhibited differentiation of adult progenitors, whereas attenuation of Notch signals and forced expression of Ngn2 significantly enhanced neurogenesis. These results suggest that both the intrinsic properties of adult progenitors and local environmental signals, including Notch signaling, account for the limited regenerative potential of the adult spinal cord.

Original languageEnglish
Pages (from-to)9814-9823
Number of pages10
JournalJournal of Neuroscience
Volume21
Issue number24
Publication statusPublished - 2001 Dec 15

Keywords

  • Adult neurogenesis
  • Injury
  • Neural progenitor
  • Notch signaling
  • Regeneration
  • Spinal cord
  • Stem cell
  • Transcription factor

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Yamamoto, S. I., Nagao, M., Sugimori, M., Kosako, H., Nakatomi, H., Yamamoto, N., Takebayashi, H., Nabeshima, Y. I., Kitamura, T., Weinmaster, G., Nakamura, K., & Nakafuku, M. (2001). Transcription factor expression and notch-dependent regulation of neural progenitors in the adult rat spinal cord. Journal of Neuroscience, 21(24), 9814-9823.