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MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis
Cell Reports, Issue: 2, Volume: 17, Pages: 469-483. | 2016-01-10
0 Patent citations    11 Scholarly citations     Reference Count: 61
Francisca F Vasconcelos;Alessandro Sessa;Catia Laranjeira;Alexandre A S F Raposo;Vera Teixeira;Daniel W Hagey;Diogo M Tomaz;Jonas Muhr;Vania Broccoli;Diogo S Castro

摘要

Summary 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.


机构

Instituto Gulbenkian de Ciência;Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.Seattle Children's Research Institute;Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.Instituto Gulbenkian de Ciência;Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.Instituto Gulbenkian de Ciência;Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.Instituto Gulbenkian de Ciência;Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.Ludwig Institute for Cancer Research;Department of Cell and Molecular Biology, Ludwig Institute for Cancer Research, Karolinska Institutet, 17177 Stockholm, Sweden.Instituto Gulbenkian de Ciência;Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.Ludwig Institute for Cancer Research;Department of Cell and Molecular Biology, Ludwig Institute for Cancer Research, Karolinska Institutet, 17177 Stockholm, Sweden.National Research Council;Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.Instituto Gulbenkian de Ciência;Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal. Electronic address: dscastro@igc.gulbenkian.pt.


文献类型:

journal article;

出版商:

Cell Press

发表时间:

2016-01-10

基金信息