MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis
نویسندگان
چکیده
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.
منابع مشابه
Adult Hippocampal Neurogenesis and Memory
Adult neurogenesis, a concept emergent in the late 1990s, is the generation of new neurons in the adult brain. This process occurs thank to cells who have this proliferative feature, named as Neural Stem Cells (NSCs). Neural Stem Cells (NSCs) are primary progenitors who can generate the two neural types (neurons and glia). Classically it was assumed that NSCs are only present in the embryo, but...
متن کاملAdult Hippocampal Neurogenesis and Memory
Adult neurogenesis, a concept emergent in the late 1990s, is the generation of new neurons in the adult brain. This process occurs thank to cells who have this proliferative feature, named as Neural Stem Cells (NSCs). Neural Stem Cells (NSCs) are primary progenitors who can generate the two neural types (neurons and glia). Classically it was assumed that NSCs are only present in the embryo, but...
متن کاملNotch in the Vertebrate Nervous System: An Old Dog with New Tricks
The Notch pathway is prominent among those known to regulate neural development in vertebrates. Notch receptor activation can inhibit neurogenesis, maintain neural progenitor character, and in some contexts promote gliogenesis and drive binary fate choices. Recently, a wave of exciting studies has emerged, which has both solidified previously held assertions and expanded our understanding of No...
متن کاملPAR-1 phosphorylates Mind bomb to promote vertebrate neurogenesis.
Generation of neurons in the vertebrate central nervous system requires a complex transcriptional regulatory network and signaling processes in polarized neuroepithelial progenitor cells. Here we demonstrate that neurogenesis in the Xenopus neural plate in vivo and mammalian neural progenitors in vitro involves intrinsic antagonistic activities of the polarity proteins PAR-1 and aPKC. Furthermo...
متن کامل