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

Genes Dev. 2020 Dec 1;34(23-24):1666-1679. doi: 10.1101/gad.342212.120. Epub 2020 Nov 12.


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 (CO2) and, in a context-dependent manner, switch from mediating avoidance of CO2 to supporting CO2 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 CO2 and regulates expression of a subset of BAG-specific genes. Unlike ets-5 mutants, which are defective for both attraction to and avoidance of CO2, 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.

Keywords: C. elegans; ETS transcription factor; chemosensation; neurodevelopment; nuclear receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Gene Expression Regulation / genetics
  • Neuronal Plasticity / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Sensory Receptor Cells / cytology*
  • Sensory Receptor Cells / metabolism*


  • Caenorhabditis elegans Proteins
  • Receptors, Cytoplasmic and Nuclear