Temporal transitions in the post-mitotic nervous system of Caenorhabditis elegans

In most animals, the majority of the nervous system is generated and assembled into neuronal circuits during embryonic development1. However, during juvenile stages, nervous systems still undergo extensive anatomical and functional changes to eventually form a fully mature nervous system by the adult stage2,3. The molecular changes in post-mitotic neurons across post-embryonic development and the genetic programs that control these temporal transitions are not well understood4,5. Here, using the model system Caenorhabditis elegans, we comprehensively characterized the distinct functional states (locomotor behaviour) and the corresponding distinct molecular states (transcriptome) of the post-mitotic nervous system across temporal transitions during post-embryonic development. We observed pervasive, neuron-type-specific changes in gene expression, many of which are controlled by the developmental upregulation of the conserved heterochronic microRNA LIN-4 and the subsequent promotion of a mature neuronal transcriptional program through the repression of its target, the transcription factor lin-14. The functional relevance of these molecular transitions are exemplified by a temporally regulated target gene of the LIN-14 transcription factor, nlp-45, a neuropeptide-encoding gene, which we find is required for several distinct temporal transitions in exploratory activity during post-embryonic development. Our study provides insights into regulatory strategies that control neuron-type-specific gene batteries to modulate distinct behavioural states across temporal, sexual and environmental dimensions of post-embryonic development.