Pheromone regulation of gene expression in the brain

信息素对大脑基因表达的调节

• 批准号: 6906607
• 负责人: GENE E ROBINSON
• 金额: $ 27.85万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6906607
• 关键词: Drosophilidae; Hymenoptera; RNA interference; behavioral /social science research tag; behavioral genetics; bioinformatics; brain; chromatin immunoprecipitation; ethology; gel mobility shift assay; gene expression; gene induction /repression; green fluorescent proteins; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; microarray technology; neural plasticity; neuroanatomy; pheromone; polymerase chain reaction; protein sequence; social behavior; synapses; tissue /cell culture; transcription factor; Drosophilidae; Hymenoptera; RNA interference; behavioral /social science research tag; behavioral genetics; bioinformatics; brain; chromatin immunoprecipitation; ethology; gel mobility shift assay; gene expression; gene induction /repression; green fluorescent proteins; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; microarray technology; neural plasticity; neuroanatomy; pheromone; polymerase chain reaction; protein sequence; social behavior; synapses; tissue /cell culture; transcription factor

DESCRIPTION (provided by applicant): We will couple a novel model (honey bee) with powerful new genomic resources (cDNA microarray and a soon-to-be-completed complete genome sequence) to study how pheromones regulate gene expression in the brain. Endocrine-mediated behavioral development in the bee is regulated in a manner strikingly similar to the regulation of mammalian reproductive development, by primer pheromones, and honeybee queen mandibular pheromone (QMP) is one of the few chemically characterized primer pheromones known to affect endocrine-mediated physiological and behavioral development. We will: 1) Determine how Kr-hl expression is related to pheromone regulation of behavior, Kr-ht, the first pheromone regulated gene identified in a higher brain center, is a transcription factor and is regulated in two socially relevant ways. We will test the hypothesis that QMP repression of Kr-hl expression is related to this pheromone's inhibitory effects on endocrine-mediated behavioral maturation with a set of social, behavioral, and pharmacological manipulations. 2) Determine the effect of Kr-hl expression on brain cell neuroanatomy and synaptic structure using immunocytochemistry and the powerful MARCM technique in Drosophila and complementary approaches in bee (with Tzumin Lee). 3) Identify downstream targets of Kr-ht transcriptional regulation. As a transcription factor, Kr-hl presumably functions by controlling expression of other genes that would play more direct functional roles in neuronal remodeling or regulating foraging behavior. We will use a multi-pronged approach to identify these genes involving, identification the consensus binding sequence of the bee and Drosophila Kr-hl proteins; bioinformatics (with Hugh Robertson); characterization of proteins associated with Kr-hl by peptide sequencing and chromatin remodeling assays; microarray experiments in both bees and flies; and chromatin immunoprecipitation (with Craig Mizzen) The principal significance of this research is that it will improve our molecular understanding of how chemical communication influences neural and behavioral plasticity.

描述（由申请人提供）：我们将将一种新型模型（Honey Bee）与强大的新基因组资源（cDNA微阵列和即将完成的完整基因组序列）进行研究，以研究信息素如何调节大脑中的基因表达。蜜蜂中内分泌介导的行为发展的调节方式与引物信息素的调节，与哺乳动物生殖发育的调节非常相似，而Honeybee Queen Queen beend primak ofendibular terlomone（QMP）是少数已知的化学特征性启动蛋白酶之一。我们将：1）确定KR-HL表达与行为的信息素调控是如何相关的，KR-HT是在较高大脑中心鉴定的第一个信息素调节基因，是转录因子，并以两种社会相关的方式进行调节。我们将检验以下假设：QMP抑制KR-HL表达与该信息素对内分泌介导的行为成熟的抑制作用有关，并具有一组社会，行为和药理操作。 2）使用免疫细胞化学和果蝇中强大的MARCM技术确定KR-HL表达对脑细胞神经解剖结构和突触结构的影响，以及蜜蜂（带有Tzumin Lee）中的互补方法。 3）确定KR-HT转录调控的下游目标。作为转录因子，KR-HL可能通过控制其他基因的表达来起作用，这些基因在神经元重塑或调节觅食行为中起着更直接的功能作用。我们将使用一种多管态的方法来识别涉及的这些基因，鉴定蜜蜂和果蝇KR-HL蛋白的共有结合序列；生物信息学（与休·罗伯逊（Hugh Robertson）一起）；通过肽测序和染色质重塑测定法对与KR-HL相关的蛋白质的表征；蜜蜂和果蝇的微阵列实验；和染色质免疫沉淀（带有Craig Mizzen）这项研究的主要意义在于，它将提高我们对化学通信如何影响神经和行为可塑性的分子理解。