PMID- 10648228 OWN - NLM STAT- MEDLINE DCOM- 20000317 LR - 20220215 IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 127 IP - 4 DP - 2000 Feb TI - Generation of neurons by transient expression of neural bHLH proteins in mammalian cells. PG - 693-702 AB - 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. FAU - Farah, M H AU - Farah MH AD - Mental Health Research Institute, Neuroscience Program, and Department of Biology, University of Michigan, Ann Arbor, MI 48104-1687, USA. FAU - Olson, J M AU - Olson JM FAU - Sucic, H B AU - Sucic HB FAU - Hume, R I AU - Hume RI FAU - Tapscott, S J AU - Tapscott SJ FAU - Turner, D L AU - Turner DL LA - eng GR - P30 HD28834/HD/NICHD NIH HHS/United States GR - R01NS36086/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (Ascl1 protein, mouse) RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Cdkn1b protein, mouse) RN - 0 (Cell Cycle Proteins) RN - 0 (DNA Primers) RN - 0 (DNA-Binding Proteins) RN - 0 (Microtubule-Associated Proteins) RN - 0 (NEUROD2 protein, human) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurod2 protein, mouse) RN - 0 (Neuropeptides) RN - 0 (Transcription Factors) RN - 0 (Tumor Suppressor Proteins) RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27) RN - 182238-50-2 (Neurog1 protein, mouse) RN - EC 2.7.11.22 (Cyclin-Dependent Kinases) SB - IM MH - Animals MH - Base Sequence MH - Basic Helix-Loop-Helix Transcription Factors MH - Cell Cycle MH - *Cell Cycle Proteins MH - Cell Differentiation MH - Cell Line MH - Cyclin-Dependent Kinase Inhibitor p27 MH - Cyclin-Dependent Kinases/antagonists & inhibitors MH - DNA Primers/genetics MH - DNA-Binding Proteins/genetics MH - Gene Expression Regulation, Developmental MH - Genetic Vectors MH - Helix-Loop-Helix Motifs/*genetics MH - Mice MH - Microtubule-Associated Proteins/genetics MH - Nerve Tissue Proteins/genetics MH - Neurons/*cytology/*metabolism MH - Neuropeptides/genetics MH - Transcription Factors/*genetics MH - Transfection MH - *Tumor Suppressor Proteins EDAT- 2000/01/29 09:00 MHDA- 2000/03/25 09:00 CRDT- 2000/01/29 09:00 PHST- 2000/01/29 09:00 [pubmed] PHST- 2000/03/25 09:00 [medline] PHST- 2000/01/29 09:00 [entrez] AID - 10.1242/dev.127.4.693 [doi] PST - ppublish SO - Development. 2000 Feb;127(4):693-702. doi: 10.1242/dev.127.4.693.