Epigenetic regulation of social and behavioral plasticity in ants

蚂蚁社会和行为可塑性的表观遗传调控

• 批准号: 10707189
• 负责人: Roberto Bonasio
• 金额: $ 40.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707189
• 关键词: Adult; Aggressive behavior; Antibodies; Ants; Behavior; Behavior Disorders; Behavioral; Behavioral Assay; Biochemical; Biological Models; Brain; Castes; Cells; Chromatin; Chromatin Structure; Cues; Data; Discipline of Nursing; ERG gene; Epigenetic Process; Gene Expression; Genes; Genetic Transcription; Genome; Genomic approach; Goals; Gonadotropin Hormone Releasing Hormone; Homologous Gene; Human; Immunofluorescence Immunologic; Impaired cognition; In Situ Hybridization; Insecta; Mammals; Mental Retardation; Mental disorders; Metabolism; Modeling; Molecular; Neurodevelopmental Disorder; Neurons; Neuropeptides; Pathway interactions; Phenotype; Physiology; Process; Proteins; Publishing; Regulation; Repression; Reproduction; Role; Social Behavior; Social Environment; Specific qualifier value; Testing; Vasopressin Receptor; Vasopressins; Work; behavioral genomics; behavioral plasticity; egg; epigenetic regulation; experience; experimental study; functional genomics; genetic approach; genetic manipulation; in vivo; insight; pharmacologic; prevent; programs; response; single-cell RNA sequencing; social; transcription factor; transcriptome sequencing

ABSTRACT The goal of this proposal is to determine how epigenetic pathways regulate plasticity in social behaviors using the model ant Harpegnathos saltator. Specifically, we will test the hypothesis that external social cues are conveyed to chromatin by neuropeptides that regulate downstream transcription factors and associated epigenetic pathways to enable stable changes in social behavior. Epigenetic pathways are often disrupted in neurodevelopmental and behavioral disorders. Harpegnathos ants are an ideal model system to study brain epigenetics because workers and queens have the same genes but display distinct social behaviors. Furthermore, adult Harpegnathos workers can become queens via a remarkable phenotypic transition that involves plastic changes in reproduction, metabolism, and behavior. We have discovered that the ant homolog of the human gonadotropin-releasing hormone, the neuropeptide corazonin, is downregulated as Harpegnathos workers become queens and showed that it is necessary and sufficient to stimulate hunting in workers. Our preliminary data show that vasopressin, a neuropeptide with conserved social roles in mammals, is also preferentially expressed in worker brains, especially in those who do not express high levels of corazonin. In Aim 1, we will determine whether these two neuropeptides act on distinct or overlapping neuronal, molecular, and epigenetic pathways and whether they drive distinct social behaviors. Our previous work also revealed that Kr-h1, a transcription factor induced by corazonin, prevents unscheduled activation of “socially inappropriate” genes in the brain, thereby maintaining proper social behavior in both workers and gamergates. Preliminary studies identified another transcription factor, Fd3F, which is repressed by corazonin and might promote social plasticity in opposition to Kr-h1. Fd3F shares homology with pioneer transcription factors in other species, suggesting that an ability to reprogram chromatin states might underpin its function in behavioral reprogramming. In Aim 2, we will identify the changes on transcription and chromatin by which these transcription factors regulate brain and behavioral plasticity during adult caste transitions in Harpegnathos. The proposed experiments will leverage our previous experience with in vivo manipulation of gene expression in ant brains followed by behavioral and functional genomics analyses. Given that the neuropeptides, transcription factors, and epigenetic regulators investigated in this proposal are deeply conserved, our results should have broad impact on our understanding of how these molecular processes regulate social behavior.

抽象的 该提案的目标是确定表观遗传途径如何调节社会行为的可塑性 使用模型蚂蚁 Harpegnathos saltator。具体来说，我们将检验以下假设：外部社交线索 通过调节下游转录因子和相关的神经肽传递至染色质 表观遗传途径能够实现社会行为的稳定变化。 表观遗传途径经常在神经发育和行为障碍中被破坏。哈佩尼亚托斯 蚂蚁是研究大脑表观遗传学的理想模型系统，因为工蚁和蚁后具有相同的基因 但表现出独特的社交行为。此外，成年 Harpegnathos 工人可以通过以下方式成为女王： 显着的表型转变涉及生殖、新陈代谢和行为的可塑性变化。 我们发现，人类促性腺激素释放激素的蚂蚁同源物，神经肽 随着 Harpegnathos 工蜂成为蜂王，corazonin 的含量被下调，这表明它是必要且有效的 足以刺激工人们的狩猎。我们的初步数据表明，加压素（一种神经肽） 哺乳动物中保守的社会角色也优先在工人大脑中表达，特别是在那些 不表达高水平的 corazonin。在目标 1 中，我们将确定这两种神经肽是否作用于 不同或重叠的神经元、分子和表观遗传途径，以及它们是否驱动不同的社会 行为。 我们之前的工作还表明，Kr-h1（一种由 corazonin 诱导的转录因子）可以防止意外发生。 激活大脑中“不适宜社交”的基因，从而维持正常的社交行为 工人和玩家门。初步研究发现了另一种转录因子 Fd3F，该因子受到抑制 与 Kr-h1 相反，它可能会促进社会可塑性。 Fd3F 与先锋具有同源性 其他物种中的转录因子，表明重新编程染色质状态的能力可能是基础 它在行为重编程中的功能。在目标 2 中，我们将识别转录和染色质的变化 这些转录因子通过这些转录因子在成人种姓转变过程中调节大脑和行为可塑性 哈佩尼亚托斯。 拟议的实验将利用我们之前在体内基因表达操作方面的经验 在蚂蚁大脑中进行行为和功能基因组学分析。鉴于神经肽， 本提案中研究的转录因子和表观遗传调节因子是高度保守的，我们的结果 应该对我们对这些分子过程如何调节社会行为的理解产生广泛的影响。