Genetics of Corticotroph Development in Zebrafish

斑马鱼促肾上腺皮质激素发育的遗传学

• 批准号: 7256231
• 负责人: NING-AI LIU
• 金额: $ 12.36万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7256231
• 关键词: Accounting; Affect; Anatomy; Anterior; Anterior Pituitary Gland; Award; Basic Science; Candidate Disease Gene; Cell Lineage; Cells; Clinical; Cloning; Commit; Corticotropin; Development; Developmental Biology; Diagnosis; Doctor of Medicine; Doctor of Philosophy; Dominant-Negative Mutation; Embryo; Embryology; Endocrine; Endocrinology; Environment; Essential Genes; Ethylnitrosourea; Event; Excision; Faculty; Failure; Fellowship; Fertilization; Fishes; Fluorescence; Funding; Future; Genes; Genetic; Genetic Screening; Green Fluorescent Proteins; Growth; Histologic; Hormones; Hour; Human; Hydrocortisone; Hypophyseal diverticulum; Knowledge; Life; Mediating; Medical center; Medicine; Mentors; Molecular; Molecular Biology; Molecular Genetics; Morbidity - disease rate; Mutation; Operative Surgical Procedures; Organ; Pathogenesis; Pathway interactions; Pharmacotherapy; Phenotype; Physicians; Pituitary Corticotropin Secreting Adenoma; Pituitary Gland; Pituitary Gland Adenoma; Pituitary Neoplasms; Pituitary-dependent Cushing' s disease; Pro-Opiomelanocortin; Proteins; Recurrence; Regulatory Pathway; Relative (related person); Research; Research Proposals; Research Training; Role; Side; Signaling Molecule; Stat3 protein; System; Testing; Tissues; Training; Transgenes; Transgenic Organisms; Tumor-Derived; Zebrafish; adenoma; career; genetic analysis; human disease; in vivo; in vivo Model; interest; loss of function mutation; mortality; mutant; neoplastic cell; programs; promoter; protein expression; transcription factor; tumor

DESCRIPTION (provided by applicant): Corticotroph ontogeny during vertebrate development involves molecular pathways distinct from other pituitary cell lineages. The critical determinants of corticotroph differentiation remain largely unclear. Both transcription factors and soluble molecules signaling via Jak/STAT pathways are involved in corticotroph development and pro-opiomelanocortin (POMC) expression. Using POMC expression as an entry point, I propose to study genetic and molecular mechanisms underlying corticotroph determination and differentiation in zebrafish. The aims of this K08 proposal are (1) to elucidate the critical roles of STAT 3 in POMC lineage development; (2) to perform a genetic screen to identify and characterize essential genes required for development of POMC lineage. The latter aim will be achieved through participation in a NIH-funded organ-specific genetic screen that utilizes live transgenic zebrafish harboring fluorescent tissues. Transgenic zebrafish expressing green fluorescent protein driven by the POMC promoter offer a unique in vivo model allowing a detailed genetic analysis of POMC-specific cells in living embryos. As the candidate for this proposal, I am currently a fellow in the Division of Endocrinology, Cedars- Sinai Medical Center (CSMC), UCLA and will complete my fellowship in June 2003. Through the proposed studies, I will expand my knowledge of general and neuro- endocrinology, especially pituitary developmental biology, and further a broad training in molecular biology, genetics, embryology and endocrinology. By the end of this award, I will be eminently trained to undertake independent basic research in pituitary development and to pursue a productive research career in academic medicine. The faculty at CSMC and UCLA have excellent reputations in both strong basic research and training physicians to develop independent careers in academic medicine. I will be mentored by both endocrine and developmental biology faculty at CSMC and UCLA, which will provide synergistic enrichment for this K08 application. CSMC has well-established programs related to my proposal and research interests and is fully committed to sustain my research career development in an environment of academic excellence.

描述（由申请人提供）： 脊椎动物发育过程中的促肾上腺皮质激素个体发育涉及与其他垂体细胞谱系不同的分子途径。促肾上腺皮质激素细胞分化的关键决定因素在很大程度上仍不清楚。通过 Jak/STAT 途径发出信号的转录因子和可溶性分子都参与促肾上腺皮质激素细胞的发育和阿片黑皮质素原 (POMC) 的表达。我建议以 POMC 表达为切入点，研究斑马鱼促肾上腺皮质激素决定和分化的遗传和分子机制。该 K08 提案的目的是（1）阐明 STAT 3 在 POMC 谱系发展中的关键作用； (2) 进行遗传筛选，以鉴定和表征 POMC 谱系发育所需的必需基因。后一个目标将通过参与美国国立卫生研究院资助的器官特异性遗传筛选来实现，该筛选利用带有荧光组织的活体转基因斑马鱼。表达由 POMC 启动子驱动的绿色荧光蛋白的转基因斑马鱼提供了独特的体内模型，允许对活体胚胎中 POMC 特异性细胞进行详细的遗传分析。 作为本提案的候选人，我目前是加州大学洛杉矶分校雪松西奈医学中心 (CSMC) 内分泌科的研究员，并将于 2003 年 6 月完成我的研究金。通过拟议的研究，我将扩展我对普通内分泌学和神经内分泌学，特别是垂体发育生物学的知识，并进一步接受分子生物学、遗传学、胚胎学和内分泌学方面的广泛培训。到这个奖项结束时，我将受到良好的培训，能够进行垂体发育的独立基础研究，并在学术医学领域从事富有成效的研究生涯。 CSMC 和加州大学洛杉矶分校的教师在强大的基础研究和培训医生以发展学术医学的独立职业方面都享有盛誉。我将得到 CSMC 和 UCLA 内分泌和发育生物学教师的指导，这将为这个 K08 应用提供协同丰富的内容。华润上华拥有与我的提案和研究兴趣相关的完善项目，并完全致力于在卓越的学术环境中维持我的研究职业发展。