Mechanisms regulating GABAergic neurogenesis in the developing mouse midbrain

In this study, we provide molecular, genetic and phenotypic evidence for the unique, overlapping and synergistic interaction between the hairy Enhancer of split-related [h/E(spl)] transcription factor (TF) MEGANE (MGN, HELT, HESLIKE) and the proneural TF MASH1 (ASCL1) for the acquisition of midbrain GABAergic identity. By combination of gain- and loss-of-function experiments in the developing mouse midbrain, we discovered a novel dorsal/ventral specification mechanism by which MGN and MASH1 cooperation induces GABAergic identity. These results provide a novel paradigm how [h/E(spl)] and proneural families can cooperate for the acquisition of midbrain GABAergic neuronal identity.