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Published on: June 8, 2018
MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis
Francisca F Vasconcelos1, Alessandro Sessa2, Cátia Laranjeira1
1Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
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.
Insights
Ascl1 triggers MyT1, a transcription factor that suppresses neural progenitor genes and promotes neuron generation by inhibiting Notch signaling. This discovery reveals a key mechanism coupling neuronal differentiation with the silencing of progenitor cell identity.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Neuronal differentiation involves significant gene expression changes driven by transcription factors like Ascl1.
- While Ascl1's role in activating differentiation genes is known, mechanisms suppressing progenitor identity are less understood.
Purpose of the Study:
- To investigate how Ascl1 suppresses neural progenitor identity during neurogenesis.
- To identify downstream targets and mechanisms regulated by Ascl1 in neuronal differentiation.
Main Methods:
- Functional studies of MyT1 during neurogenesis.
- Transcriptional program characterization of MyT1.
- Analysis of MyT1 binding and its effect on gene transcription.
Main Results:
- Ascl1 induces the transcription factor MyT1, promoting neuronal differentiation.
- MyT1 represses gene transcription in neural progenitor cells.
- MyT1 counteracts Notch signaling by targeting Notch1 and downstream targets like Hes1, Sox2, Id3, and Olig1.
Conclusions:
- Ascl1 suppresses progenitor cell fate by inducing MyT1, which acts cell-autonomously.
- MyT1 couples neuronal differentiation with the repression of progenitor identity via Notch signaling inhibition.
