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: 10567966
• 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/10567966
• 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; Pharmacology; Phenotype; Physiology; Process; Proteins; Publishing; Regulation; 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; 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 该提议的目的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盐盐。具体而言，我们将检验外部社会提示的假设 通过调节下游转录因子和相关的神经肽将染色质传送到染色质 表观遗传学途径可以使社会行为稳定变化。 在神经发育和行为障碍中，表观遗传途径通常是残疾的。 Harpegnathos 蚂蚁是研究大脑表观遗传学的理想模型系统，因为工人和皇后具有相同的基因 但是显示出不同的社会行为。此外，成人harpegnathos工人可以通过 显着的表型过渡，涉及塑性变化，代谢和行为。 我们发现人促性腺激素释放的马龙，神经肽的蚂蚁同源物 Corazonin被下调，因为Harpegnathos工人成为皇后，并表明这是必要的，并且 足以刺激工人的狩猎。我们的初步数据表明，加压素是一种神经肽 在哺乳动物中保守的社会角色，在工人的大脑中也优先表达 请勿表达高水平的corazonin。在AIM 1中，我们将确定这两种神经肽是否作用于 独特或重叠的神经元，分子和表观遗传途径以及它们是否推动不同的社交 行为。 我们以前的工作还表明，corazonin诱导的转录因子KR-H1可防止未定的转录因子 激活大脑中的“社会不恰当”基因，从而维持两者的适当社会行为 工人和游戏。初步研究确定了另一个转录因子FD3F，该因子表示为 Corazonin的作者，可能会促进反对KR-H1的社会可塑性。 FD3F与先驱分享同源性 其他物种中的转录因子，表明可以重新编程染色质状态的能力可能支持 它在行为重编程中的功能。在AIM 2中，我们将确定转录和染色质的更改 这些转录因子在成人种姓转变期间调节大脑和行为可塑性 Harpegnathos。 提出的实验将利用我们以前在体内操纵基因表达的经验 在蚂蚁大脑中，随后进行了行为和功能基因组学分析。鉴于神经肽， 转录因子和该提案中研究的表观遗传调节剂是深处的，我们的结果是 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。