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During development, the nervous system generates neurons that serve highly specialized roles and, accordingly, possess unique functional attributes. The chemosensory BAG neurons of  C. elegans  are striking exemplars of this. BAGs sense the respiratory gas carbon dioxide (CO 2 ) and, in a context-dependent manner, switch from mediating avoidance of CO 2  to supporting CO 2  attraction. To determine mechanisms that support the physiology and plasticity of BAG neurons, we used tandem ChIP-seq and cell targeted RNA-seq to identify gene targets of the transcription factor ETS-5, which is required for BAG development. A functional screen of ETS-5 targets revealed that NHR-6, the sole  C. elegans  NR4A-type nuclear receptor, is required for BAG-mediated avoidance of CO 2  and regulates expression of a subset of BAG-specific genes. Unlike  ets-5  mutants, which are defective for both attraction to and avoidance of CO 2 ,  nhr-6  mutants are fully competent for attraction. These data indicate that the remarkable ability of BAGs to adaptively assign positive or negative valence to a chemosensory stimulus requires a gene-regulatory program supported by an evolutionarily conserved type of nuclear receptor. We suggest that NHR-6 might be an example of a developmental mechanism for modular encoding of functional plasticity in the nervous system.

Development of specialized sensory neurons engages a nuclear receptor required for functional plasticity