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

基本信息

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
项目类别：
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

项目摘要

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具体来说，我们将使用 Harpegnathos saltator 模型来检验外部社交线索的假设。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。在神经发育和行为障碍中，表观遗传途径经常受到破坏。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会行为此外，成年哈佩纳托斯工人可以通过以下方式成为女王。一种显着的表型转变，涉及繁殖、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 工蜂成为蜂后，corazonin 的含量被下调，这表明它是必要且有效的我们的初步数据表明，加压素（一种神经肽）足以刺激工蜂的狩猎。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、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，由 corazonin 诱导的转录因子 Kr-h1 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初步研究发现了另一种转录因子 Fd3F，该因子受到抑制。与 Fd3F 相比，可能会促进社会可塑性，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鉴于神经肽，随后进行了行为和功能基因组学分析。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。