Developmental Regulation of Brain and Behavior

大脑和行为的发育调节

• 批准号: 7624630
• 负责人: JULI S. WADE
• 金额: $ 30.75万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7624630
• 关键词: Acute; Address; Adolescent; Age; Aging; Androgen Receptor; Androgens; Area; Behavior; Birds; Brain; Brain region; Bromodeoxyuridine; Cell Nucleus; Cells; Characteristics; Chickens; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 13; Code; Development; Disease; Estradiol; Estrogens; Female; Funding; Gene Expression; Genes; Gonadal Steroid Hormones; In Situ Hybridization; Individual; Injection of therapeutic agent; Injury; Lead; Learning; Literature; Location; Mammals; Measures; Messenger RNA; Modeling; Morphology; Nature; One-Step dentin bonding system; Printing; Process; Proliferating; Prosencephalon; Proteins; Regulation; Ribosomal Proteins; Role; Sequence Analysis; Sex Characteristics; Sex Chromosomes; Solutions; Source; Staging; Steroids; Structure; System; Testing; Time; Up-Regulation; Validation; Vertebrates; Work; Zinc Fingers; base; brain behavior; cDNA Arrays; gene function; genetic regulatory protein; hatching; interest; lateral ventricle; male; protein expression; relating to nervous system; response; ribosomal protein L17; secretory carrier membrane protein 1; steroid hormone; zebra finch

DESCRIPTION (provided by applicant): The proposed studies will elucidate the roles of five genes and their protein products in the development of brain and behavior. They focus on sexual differentiation of the structure and function of the song control system in the forebrain of zebra finches. Only males sing, and the brain areas that control song are far larger in males, which is due to males having more and larger cells in these regions than females. In many vertebrates, the development of these types of male-biased differences in behavior and morphology is regulated mainly by gonadal steroids. However, in some mammalian systems, sexual differentiation is controlled more directly by the expression of genes. In zebra finches, the evidence suggests that both are involved. The present proposal will test the hypothesis that masculinization of the zebra finch song system is controlled by genes, including those on the Z-chromosome (unlike XX/XY mammals, male zebra finches are ZZ and females are ZW), that influence the response of the brain to steroid hormones. The work involves characterization of five genes we recently identified in the zebra finch brain with enhanced expression in song control nuclei in males compared to females. These genes include those encoding ribosomal proteins L17 and L37, secretory carrier membrane protein 1 (SCAMP1), zinc finger protein 216 (ZNF216) and a COBW-domain containing protein. We will complete the sequence analysis for these genes, confirm their locations on zebra finch chromosomes, and determine the time-course of their sexually dimorphic expression within the song circuit and related regions. The effects of inhibiting their function on development of song learning and masculinization of song system morphology will be elucidated. In addition, interactions between the genes and steroid hormone will be investigated. For example, the role of estradiol in the expression of the genes and potential interactions with androgen receptors, both of which are involved in masculinization, will be studied. Very little information is available in the literature on these genes, so as this work is pursued, we will learn not only more about mechanisms regulating sexual differentiation, but also about the genes themselves. Most importantly, however, the proposed studies will elucidate mechanisms critical for normal development of brain structure and function, and can lead to the discovery of solutions to problems, including those associated with disease, injury, aging and contaminant exposure.

描述（由申请人提供）：拟议的研究将阐明五个基因及其蛋白质产物在大脑和行为发展中的作用。他们专注于在斑马雀科前脑中歌曲控制系统的结构和功能的性差异。只有雄性唱歌，而控制歌曲的大脑区域在男性中的大得多，这是由于这些地区的男性比女性具有更多和更大的细胞。在许多脊椎动物中，这些类型的行为和形态差异的发展主要由性腺类固醇调节。但是，在某些哺乳动物系统中，性别分化更直接地通过基因的表达来控制。在斑马雀科中，证据表明两者都参与其中。本提案将检验以下假设：斑马雀科系统的男性化由基因控制，包括Z染色体上的基因（与XX/XY哺乳动物不同，雄性斑马雀科是ZZ，而女性则是ZW，而女性则是ZW），它们会影响大脑对类固醇激素的反应。与女性相比，这项工作涉及我们最近在斑马芬奇大脑中鉴定出的五个基因，在歌曲控制核中的表达增强。这些基因包括那些编码核糖体蛋白L17和L37的基因，分泌载体膜蛋白1（SCAMP1），锌指蛋白216（ZNF216）和含有蛋白质的COBW-DOMAIN。我们将完成这些基因的序列分析，确认其在斑马雀科染色体上的位置，并确定其在歌曲电路和相关区域中其性二态表达的时间顺序。抑制其功能对歌曲学习发展和歌曲系统形态的男性化的影响将得到阐明。另外，将研究基因与类固醇激素之间的相互作用。例如，将研究雌二醇在基因表达中的作用以及与雄激素受体的潜在相互作用（两者都参与男性化）。有关这些基因的文献中，很少有信息，因此，随着这项工作的追求，我们不仅会了解有关调节性差异化的机制，而且还了解有关基因本身的机制。然而，最重要的是，拟议的研究将阐明对大脑结构和功能正常发展至关重要的机制，并可能导致发现解决方案的问题，包括与疾病，损伤，衰老和污染物暴露有关的问题。