Lee Harksun, Boor Sonia A, Hilbert Zoë A, Meisel Joshua D, Park Jaeseok, Wang Ye, McKeown Ryan, Fischer Sylvia E J, Andersen Erik C, Kim Dennis H
Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School; Boston, 02115, USA.
Department of Biology, Massachusetts Institute of Technology; Cambridge, 02139, USA.
bioRxiv. 2023 Sep 19:2023.09.09.556976. doi: 10.1101/2023.09.09.556976.
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. The neuroendocrine TGF-beta ligand, DAF-7, regulates diverse behavioral responses of 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 and identified common variants in , encoding a GTPase-Activating Protein homologous to mammalian SynGAP proteins, which modify expression cell-non-autonomously and promote exploratory foraging behavior in a 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.
动物行为多样性背后的分子机制尚未得到充分理解。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。神经内分泌TGF-β配体DAF-7调节对细菌食物和病原体的多种行为反应。其动态的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,我们研究了化学感觉神经元ASJ对中该基因表达的自然变异,并在一个基因中鉴定出常见变异,该基因编码一种与哺乳动物SynGAP蛋白同源的GTP酶激活蛋白,它以非细胞自主方式修饰该基因的表达,并以DAF-7依赖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,并表明介导宿主-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。