Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sci Adv. 2024 Jun 14;10(24):eadk9481. doi: 10.1126/sciadv.adk9481. Epub 2024 Jun 12.
The molecular mechanisms underlying diversity in animal behavior are not well understood. A major experimental challenge is determining the contribution of genetic variants that affect neuronal gene expression to differences in behavioral traits. In , the neuroendocrine transforming growth factor-β ligand, DAF-7, regulates diverse behavioral responses to bacterial food and pathogens. The dynamic neuron-specific expression of is modulated by environmental and endogenous bacteria-derived cues. Here, we investigated natural variation in the expression of from the ASJ pair of chemosensory neurons. We identified common genetic variants in , encoding a Ras guanosine triphosphatase (GTPase)-activating protein homologous to mammalian synaptic Ras GTPase-activating protein, which modify expression cell nonautonomously and promote exploratory foraging behavior in a partially DAF-7-dependent manner. Our data connect natural variation in neuron-specific gene expression to differences in behavior and suggest that genetic variation in neuroendocrine signaling pathways mediating host-microbe interactions may give rise to diversity in animal behavior.
动物行为多样性的分子机制尚不清楚。一个主要的实验挑战是确定影响神经元基因表达的遗传变异对行为特征差异的贡献。在这篇文章中,神经内分泌转化生长因子-β配体 DAF-7 调节了对细菌食物和病原体的多种行为反应。 的动态神经元特异性表达受环境和内源性细菌衍生信号的调节。在这里,我们研究了 ASJ 对化学感觉神经元中 的表达的自然变异。我们鉴定了 中的常见遗传变异,该基因编码一种 Ras 鸟嘌呤核苷酸三磷酸酶 (GTPase) 激活蛋白,与哺乳动物突触 Ras GTPase 激活蛋白同源,该蛋白以非细胞自主的方式修饰 表达,并以部分依赖 DAF-7 的方式促进探索性觅食行为。我们的数据将神经元特异性基因表达的自然变异与行为差异联系起来,并表明调节宿主-微生物相互作用的神经内分泌信号通路中的遗传变异可能导致动物行为的多样性。