Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system

Masa Aki Torii, Fumio Matsuzaki, Noriko Osumi, Kozo Kaibuchi, Shun Nakamura, Simona Casarosa, François Guillemot, Masato Nakafuku

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

Like other tissues and organs in vertebrates, multipotential stem cells serve as the origin of diverse cell types during genesis of the mammalian central nervous system (CNS). During early development, stem cells self-renew and increase their total cell numbers without overt differentiation. At later stages, the cells withdraw from this self-renewal mode, and are fated to differentiate into neurons and glia in a spatially and temporally regulated manner. However, the molecular mechanisms underlying this important step in cell differentiation remain poorly understood. In this study, we present evidence that the expression and function of the neural-specific transcription factors Mash-1 and Prox-1 are involved in this process. In vivo, Mash-1- and Prox-1-expressing cells were defined as a transient proliferating population that was molecularly distinct from self-renewing stem cells. By taking advantage of in vitro culture systems, we showed that induction of Mash-1 and Prox-1 coincided with an initial step of differentiation of stem cells. Furthermore, forced expression of Mash-1 led to the down-regulation of nestin, a marker for undifferentiated neuroepithelial cells, and upregulation of Prox-1, suggesting that Mash-1 positively regulates cell differentiation. In support of these observations in vitro, we found specific defects in cellular differentiation and loss of expression of Prox-1 in the developing brain of Mash-1 mutant mice in vivo. Thus, we propose that induction of Mash-1 and Prox-1 is one of the critical molecular events that control early development of the CNS.

Original languageEnglish
Pages (from-to)443-456
Number of pages14
JournalDevelopment
Volume126
Issue number3
Publication statusPublished - 1999 Feb 1
Externally publishedYes

Keywords

  • Glia
  • Mash-1
  • Neural development
  • Neuron
  • Prospero
  • Stem cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Torii, M. A., Matsuzaki, F., Osumi, N., Kaibuchi, K., Nakamura, S., Casarosa, S., Guillemot, F., & Nakafuku, M. (1999). Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system. Development, 126(3), 443-456.