Neuronal specification is a protracted process that begins with the commitment of progenitor cells and culminates with the generation of mature neurons. Many transcription factors are continuously expressed during this process, but it is presently unclear how these factors modify their targets as cells transition through different stages of specification. In olfactory bulb adult neurogenesis, the transcription factor PBX1 controls neurogenesis in progenitor cells and survival of migrating neuroblasts. Here we show that, at later differentiation stages, PBX1 also acts as a terminal selector for the dopaminergic fate. PBX1 is additionally required for the morphological maturation of dopaminergic neurons and to repress alternative interneuron fates, findings that expand the known repertoire of terminal-selector actions. Finally, we reveal that the temporal diversification of PBX1 functions in neuronal specification is achieved, at least in part, through the dynamic regulation of alternative splicing. In C. elegans, PBX/CEH-20 also acts as dopaminergic terminal selector what suggests an ancient role for PBX factors in the regulation of dopaminergic terminal differentiation.
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