title: MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis.
abstract: The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors.forename: Francisca F
authors.initials: FF
authors.lastname: Vasconcelos
authors.affiliation: Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sessa
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors.forename: Cátia
authors.initials: C
authors.lastname: Laranjeira
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors.forename: Alexandre A S F
authors.initials: AASF
authors.lastname: Raposo
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors.forename: Vera
authors.initials: V
authors.lastname: Teixeira
authors.affiliation: Department of Cell and Molecular Biology, Ludwig Institute for Cancer Research, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hagey
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors.forename: Diogo M
authors.initials: DM
authors.lastname: Tomaz
authors.affiliation: Department of Cell and Molecular Biology, Ludwig Institute for Cancer Research, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Muhr
authors.affiliation: Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Vania
authors.initials: V
authors.lastname: Broccoli
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal. Electronic address: dscastro@igc.gulbenkian.pt.
authors.forename: Diogo S
authors.initials: DS
authors.lastname: Castro
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D000072056:Transcription Factor HES-1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics / Q000254:growth & development
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051796:Inhibitor of Differentiation Proteins; D051881:Receptor, Notch1; D055748:SOXB1 Transcription Factors; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C489734:Hes1 protein, mouse; C489726:Myt1 protein, mouse; C497762:Notch1 protein, mouse; C494786:Olig1 protein, mouse; C527783:Sox2 protein, mouse; C067679:Idb3 protein, mouse
keywords: Ascl1; Hes1; MyT1; Notch signaling; Rbpj; neurogenesis; transcription