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）：类视黄度信号在神经元表型的开发和维持中很重要。当人类中断时，这会导致学习障碍。歌曲鸟类的声带学习的工作已经确定了负责控制和发展鸟类歌曲的关键大脑中心，而正确的类视黄素信号传导是这些大脑途径足够功能的一种要求。鸣禽通过听成人的导师来学习他们的歌曲，并在一段时间的反复试验中完善它们，这是类似于人类像孩子一样学习语言的过程。这项研究的这一目标是阐明类视黄素信号如何专门影响禽歌曲途径。这将通过两个具体目标来实现。第一个目的是测量已知在类视黄素信号中已知重要的基因的表达，并识别在歌曲途径中表达的基因。显示在歌曲系统中表达的基因将在细胞水平上进一步表征，以识别大脑中类视黄素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式来补充视黄酸或去除饮食中的所有视黄酸及其代谢前体，以测试这些基因在其他系统中已知的毒性反应性，并响应和调节歌曲中心中的类视黄素水平。这些结果将对影响复杂的学习行为的类维生素性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一个受视网TINOID信号传导调节的显着特征，因此目标两个将测试改变类维生素类动物信号对大脑歌曲中心内神经元出生，迁移和建立的影响。公共卫生相关性维生素A缺乏症是一个主要的人类健康问题，对认知发展产生负面影响。类视网膜类似于治疗方法来治疗痤疮并减少临时细胞白血病的增殖，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，但是这些物种不像人类那样表现出声音学习。诸如斑马雀科之类的鸣禽确实表现出声音学习，并提供了合适的模型，以测试性类维生素性信号在语音发展和学习障碍上的重要性。

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