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.

摘要 这项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 用的是跳跃蚁模型具体来说，我们将检验外部社会线索 通过调节下游转录因子的神经肽传递到染色质， 表观遗传途径，使社会行为的稳定变化。 在神经发育和行为障碍中，表观遗传途径经常被破坏。尖颌鱼属 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。 但表现出不同的社会行为。此外，成年Harpegnathos工人可以成为女王通过一个 一种显著的表型转变，涉及生殖、代谢和行为的可塑性变化。 我们已经发现，人类促性腺激素释放激素的蚂蚁同源物， corazonin，是下调，因为Harpegnathos工人成为女王，并表明这是必要的， 足以刺激工人的狩猎。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，也优先在工人的大脑中表达，特别是在那些 并不表达高水平的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。 我们以前的工作也揭示了Kr-h1，一个由corazonin诱导的转录因子， 激活大脑中“不适合社交”的基因，从而在大脑和大脑中保持适当的社交行为。 工人和玩家。初步研究确定了另一种转录因子Fd 3F，它被抑制 可能会促进社会可塑性，而不是Kr-h1。Fd 3F与Pioneer具有同源性 其他物种中的转录因子，这表明重编程染色质状态的能力可能支持 它在行为重编程中的作用在目标2中，我们将确定转录和染色质的变化 这些转录因子在成年人的种姓转换过程中调节大脑和行为的可塑性， 竖琴怪 拟议的实验将利用我们以前的经验，在体内操纵基因表达 随后进行行为和功能基因组学分析。既然神经肽， 转录因子和表观遗传调节因子的研究在这个建议是高度保守的，我们的结果 应该对我们理解这些分子过程如何调节社会行为产生广泛的影响。