Differentiation by counteracting progenitor fate

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. Diogo Castro’s group at the IGC showed that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. In the article Vasconcelos et al entitled “MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis” they 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. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.