Retinoid Signaling in Songbirds: Learned Song, Gene Expression and Neurogenesis

鸣禽中的视黄醇信号传导：习得的鸣声、基因表达和神经发生

• 批准号: 8071561
• 负责人: Christopher R Olson
• 金额: $ 5.13万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-04 至 2012-05-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8071561
• 关键词: Acne; Acute Promyelocytic Leukemia; Adolescent; Adult; Affect; All-Trans-Retinol; Anterior; Area; Behavior; Bioinformatics; Birds; Birth; Brain; Candidate Disease Gene; Cell Nucleus; Cell Survival; Cells; Child; Cognitive; Complex; Data; Development; Diet; Embryonic Development; Exhibits; Gene Expression; Genes; Goals; Growth; Health; Human; Human Development; Language Development; Learning; Learning Disabilities; Ligands; Link; Maintenance; Malnutrition; Mammals; Measures; Metabolic; Modeling; Molecular; Motor Pathways; Neuronal Differentiation; Neurons; Nutrient; Pathway interactions; Pattern; Pattern Formation; Phenotype; Play; Population; Process; Psychological reinforcement; Regulation; Retinoids; Rodent Model; Role; S-Phase Fraction; Seeds; Signal Pathway; Signal Transduction; Signaling Molecule; Songbirds; Speech Development; Synthetic Diet; System; Testing; Tretinoin; Vitamin A; Vitamin A Deficiency; Work; base; bird song; brain pathway; cell type; cognitive function; juvenile animal; mature animal; migration; morphogens; neurogenesis; neuronal replacement; relational memory; trait; transcription factor; vocal learning; zebra finch

DESCRIPTION (provided by applicant): Retinoid signaling is important in the development and maintenance of neuronal phenotypes. When disrupted in humans this results in learning disabilities. Work on vocal learning in song birds has identified the key brain centers responsible for the control and development of learned bird song, and proper retinoid signaling is one requirement for adequate function of these brain pathways. Songbirds learn their songs by listening to adult tutors, and perfect them through a period of trial and error- a process analogous to how humans learn language as children. This goal of this study is to elucidate how retinoid signaling specifically affects the avian song pathways. This will be achieved by two specific aims. The first aim is to measure the expression of genes known to be important in retinoid signaling and identify those that are expressed in the song pathway. Genes that show expression in the song system will be further characterized at the cellular level to identify the cell types and potential target areas of retinoid signaling in the brain. We will then use a synthetic diet paradigm to either supplement retinoic acid or remove all retinoic acid and its metabolic precursors from the diet to test how these genes, that are known to be retinoic responsive in other systems, respond to and regulate retinoid levels in the song centers. These results will seed a bio-informatics analysis of the retinoid signaling pathways that affect a complex learned behavior. Because neurogenesis and neuronal differentiation is a prominent trait that is regulated by retinoid signaling, aim two will test the effects that altered retinoid signaling has on rates of neuronal birth, migration and establishment within the song centers of the brain. PUBLIC HEALTH RELEVANCE Vitamin A deficiency is a major human health issue and has negative effects on cognitive development. Retinoids are also used therapeutically to treat acne and reduce the proliferation of promyelocytic leukemia, but with severe effects on human development. Rodent models are able to test effects on relational memory and spatial learning, but these species do not exhibit vocal learning as in humans. Songbirds such as the zebra finch do exhibit vocal learning and provide a suitable model to test the importance of retinoid signaling on speech development and learning disabilities.

描述（由申请人提供）：类维生素A信号传导对于神经元表型的发育和维持很重要。当人类受到干扰时，就会导致学习障碍。对鸣禽声音学习的研究已经确定了负责控制和发展鸟类鸣叫的关键大脑中枢，而适当的视黄醇信号传导是这些大脑通路充分发挥功能的要求之一。鸣禽通过听成人导师的指导来学习歌曲，并通过一段时间的尝试和错误来完善它们——这个过程类似于人类小时候学习语言的过程。本研究的目的是阐明类维生素A信号传导如何具体影响鸟类鸣叫途径。这将通过两个具体目标来实现。第一个目标是测量已知在类维生素A信号传导中重要的基因的表达，并鉴定在歌曲通路中表达的基因。在歌曲系统中表现出表达的基因将在细胞水平上得到进一步表征，以识别大脑中视黄醇信号传导的细胞类型和潜在目标区域。然后，我们将使用合成饮食范例来补充视黄酸或从饮食中去除所有视黄酸及其代谢前体，以测试这些已知在其他系统中具有视黄酸反应的基因如何响应和调节系统中的视黄酸水平。歌曲中心。这些结果将为影响复杂学习行为的类维生素A信号通路进行生物信息学分析。由于神经发生和神经元分化是受类视黄醇信号传导调节的一个显着特征，因此目标二将测试类视黄醇信号传导改变对大脑歌曲中心内神经元出生、迁移和建立速率的影响。公共卫生相关性 维生素 A 缺乏是一个主要的人类健康问题，会对认知发展产生负面影响。类维生素A还用于治疗痤疮和减少早幼粒细胞白血病的增殖，但对人类发育有严重影响。啮齿动物模型能够测试对关系记忆和空间学习的影响，但这些物种不像人类那样表现出声音学习。斑胸草雀等鸣禽确实表现出声音学习能力，并提供了一个合适的模型来测试类维生素A信号对言语发育和学习障碍的重要性。

项目成果

Long-distance retinoid signaling in the zebra finch brain.

斑胸草雀大脑中的长距离视黄醇信号传导。

• DOI: 10.1371/journal.pone.0111722
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Roeske,TinaC;Scharff,Constance;Olson,ChristopherR;Nshdejan,Arpik;Mello,ClaudioV
• 通讯作者: Mello,ClaudioV

Dynamic gene expression in the song system of zebra finches during the song learning period.

斑胸草雀鸣叫系统在鸣叫学习期间的动态基因表达。

• DOI: 10.1002/dneu.22286
• 发表时间: 2015
• 期刊: Developmental neurobiology
• 影响因子: 3
• 作者: Olson,ChristopherR;Hodges,LisaK;Mello,ClaudioV
• 通讯作者: Mello,ClaudioV