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.

中文翻译：

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专门的感觉神经元的发展参与功能可塑性所需的核受体

在发育过程中，神经系统产生的神经元起着高度特殊的作用，因此具有独特的功能属性。秀丽隐杆线虫的化学感应BAG神经元是其典范。BAG感测呼吸气体中的二氧化碳（CO ₂），并以上下文相关的方式从避免回避CO ₂转变为支持CO ₂吸引。为了确定支持BAG神经元生理和可塑性的机制，我们使用了串联ChIP-seq和细胞靶向RNA-seq来识别BAG发展所需的转录因子ETS-5的基因靶标。对ETS-5目标的功能筛选显示，唯一的秀丽隐杆线虫NHR-6NR4A型核受体是BAG介导的避免CO ₂所必需的，它调节BAG特异性基因的一个子集的表达。与ets-5突变体（既吸引和避免CO ₂均存在缺陷）不同，nhr-6突变体完全具有吸引能力。这些数据表明，BAG对化学感觉刺激自适应分配正价或负价的显着能力需要由进化保守型核受体支持的基因调控程序。我们建议NHR-6可能是神经系统功能可塑性的模块化编码发展机制的一个例子。