Generation of neurons by transient expression of neural bHLH proteins in mammalian cells

Mohamed H. Farah, James M. Olson, Holly B. Sucic, Richard I. Hume, Stephen J. Tapscott, David L. Turner

Research output: Contribution to journalArticlepeer-review

Abstract

Basic helix-loop-helix (bHLH) transcription factors are known to function during mammalian neurogenesis. Here we show that transient transfection of vectors expressing neuroD2, MASH1, ngn1 or related neural bHLH proteins, with their putative dimerization partner E12, can convert mouse P19 embryonal carcinoma cells into differentiated neurons. Transfected cells express numerous neuron-specific proteins, adopt a neuronal morphology and are electrically excitable. Thus, the expression of neural bHLH proteins is sufficient to confer a neuronal fate on uncommitted mammalian cells. Neuronal differentiation of transfected cells is preceded by elevated expression of the cyclin-dependent kinase inhibitor p27(Kip1) and cell cycle withdrawal. This demonstrates that the bHLH proteins can link neuronal differentiation to withdrawal from the cell cycle, possibly by activating the expression of p27(Kip1). The ability to generate mammalian neurons by transient expression of neural bHLH proteins should create new opportunities for studying neurogenesis and devising neural repair strategies.

Original languageEnglish (US)
Pages (from-to)693-702
Number of pages10
JournalDevelopment
Volume127
Issue number4
StatePublished - Feb 2000
Externally publishedYes

Keywords

  • Basic-helix-loop-helix
  • Mouse
  • Neuron
  • Transcription
  • p27

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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