title: Comparison of the generic neuronal differentiation and neuron subtype specification functions of mammalian achaete-scute and atonal homologs in cultured neural progenitor cells.
abstract: In the vertebrate peripheral nervous system, the proneural genes neurogenin 1 and neurogenin 2 (Ngn1 and Ngn2), and Mash1 are required for sensory and autonomic neurogenesis, respectively. In cultures of neural tube-derived, primitive PNS progenitors NGNs promote expression of sensory markers and MASH1 that of autonomic markers. These effects do not simply reflect enhanced neuronal differentiation, suggesting that both bHLH factors also specify neuronal identity like their Drosophila counterparts. At high concentrations of BMP2 or in neural crest stem cells (NCSCs), however, NGNs like MASH1 promote only autonomic marker expression. These data suggest that that the identity specification function of NGNs is more sensitive to context than is that of MASH1. In NCSCs, MASH1 is more sensitive to Notch-mediated inhibition of neurogenesis and cell cycle arrest, than are the NGNs. Thus, the two proneural genes differ in other functional properties besides the neuron subtype identities they can promote. These properties may explain cellular differences between MASH1- and NGN-dependent lineages in the timing of neuronal differentiation and cell cycle exit.
authors.affiliation: Division of Biology 216-76, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Liching
authors.initials: L
authors.lastname: Lo
authors.forename: Emma
authors.initials: E
authors.lastname: Dormand
authors.forename: Amy
authors.initials: A
authors.lastname: Greenwood
authors.forename: David J
authors.initials: DJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D017776:Autonomic Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D017344:Genes, Insect; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010525:Peripheral Nerves / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D016212:Transforming Growth Factor beta
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D003470:Culture Media; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C500942:ATOH1 protein, human; C499318:Ascl1 protein, rat; C500943:Atoh1 protein, mouse; C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; C491183:NEUROG2 protein, human; C089199:ac protein, Drosophila; C082142:ato protein, Drosophila; C089197:sc protein, Drosophila; C486336:Neurog1 protein, mouse