Mammalian interneurons are crucial for cortical function, and are formed by progenitors located in the ganglionic eminences. Mutations in exon junction complex (EJC) components are associated with a raft of human neurological disorders known to affect interneuron neurogenesis, but these links, as well as our general understanding of interneuron generation and survival, are still incompletely understood. Now, Debra Silver and colleagues analyse the role of Magoh, an EJC component, in murine interneuron development. Magoh is highly expressed in the ganglionic eminences during interneuron neurogenesis, and conditional Magoh depletion in interneuron progenitors (but not in post-mitotic migrating interneurons) reduces cortical interneuron number in a dose-dependent manner. Magoh-depleted progenitors divide less (with over one-third of progenitors failing to divide entirely) and die more. One-third of all progenitor daughter cells also undergo apoptosis, and there is a bias towards interneurons at the expense of new progenitors in the surviving daughters. Magoh loss transcriptionally upregulates two p53 signalling targets, and p53 signalling is increased in progenitors. But while deletion of p53 in Magoh haploinsufficient progenitors completely rescues cortical interneuron number, it does not in Magoh homozygous progenitors, which still show delayed mitosis. This work illuminates the role of the EJC – and thus post-transcriptional gene regulation – in interneuron development.
