MicroRNAs (miRNAs) play crucial roles in development. miR-124, for example, is abundantly expressed in the mouse brain and is necessary for proper nervous system development, but how it drives neuronal differentiation is unclear. To remedy this lack of understanding, Robert Zeller and colleagues have comprehensively analysed miR-124 expression, function and target genes in the ascidian Ciona intestinalis (see p. 4943). They report that miR-124 interacts with several signalling pathways that are involved in nervous system development. In particular, they show that a feedback interaction between miR-124 and Notch signalling regulates the epidermal-peripheral nervous system (PNS) fate choice in tail midline cells. Thus, Notch signalling silences miR-124 in epidermal midline cells, whereas in PNS midline cells miR-124 silences Notch, Neuralized and the Ciona Hairy/Enhancer-of-Split genes. Moreover, miR-124 also shapes neuronal progenitor fields by downregulating non-neural genes including 50 Brachyury-regulated notochord genes and the muscle specifier Macho-1. Overall, these results indicate that miR-124 plays a multifaceted role in cell lineage specification during nervous system development.
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