1.19Hormonal controls of zebrafish post-embryonic melanocyte development

1.19斑马鱼胚胎后黑素细胞发育的激素控制

• 批准号: 7804866
• 负责人: Sarah Kelly McMenamin
• 金额: $ 4.56万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-27 至 2013-01-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7804866
• 关键词: Adult; Affect; Amphibia; Biological Assay; Biological Metamorphosis; Cell Lineage; Cell physiology; Cells; Defect; Development; Developmental Biology; Disease; Embryo; Embryonic Development; Endocrine; Fertilization; Fishes; Future; Genes; Genetic; Genetic Screening; Goals; Health; Hormonal; Human; Insertional Mutagenesis; Link; Malignant Neoplasms; Mammals; Mediating; Mediator of activation protein; Molecular; Morphogenesis; Neonatal; Outcome; Pathway interactions; Pattern; Pigments; Process; Recruitment Activity; Research; Resources; Role; Signal Transduction; Staging; Stem cells; Syndrome; System; Testing; Thyroid Hormones; Time; Training; Transgenic Organisms; Translating; Vertebrates; Work; Zebrafish; base; cell behavior; cell type; fetal; insight; melanocyte; mutant; novel; precursor cell; programs; research study; self-renewal; stem; stem cell population; trait; vector

DESCRIPTION (provided by applicant): The long-term objective of this work is to identify genetic, cellular, and endocrine mechanisms required for post-embryonic development in vertebrates. This proposal focuses on metamorphosis of the zebrafish, which occurs between 12-28 days post-fertilization, and is analogous to human fetal and neonatal development. Among the many changes that occur during zebrafish metamorphosis is the transformation of an embryonic/early larval pigment pattern into that of the adult, a process that depends on the recruitment of latent stem cells and is likely under hormonal control. As thyroid hormone (TH) is critical for amphibian metamorphosis as well as mammalian post-embryonic development. Aim 1 will test roles for TH signaling in zebrafish somatic and pigment pattern metamorphosis. This will be accomplished using transgenic lines to block TH signals at specific times either throughout the fish or in specific cell lineages. To examine how global endocrine mediators effect local cellular processes of specification and morphogenesis, Aim 2 will test for interactions between TH signals and Wnt signals that are known to be critical for pigment cell 'development as well as stem cell self-renewal. These experiments will employ transgenic lines and other approaches to inhibit or stimulate these pathways and assay pathway activity and phenotypic outcomes. Finally, there may be many additional mediators of post-embryonic development, and to identify these, aim 3 will constitute a forward genetic screen for mutants that fail to undergo metamorphosis either entirely or have defects in the metamorphosis of specific traits and cell types. This screen will employ gene-breaking vectors and transposon-mediated insertional mutagenesis, allowing the efficient identification and analysis of affected loci. Together these efforts will provide significant new insights into the mechanisms of vertebrate post-embryonic development. *Vertebrates undergo extensive changes during postembryonic stages and many of these changes depend on the recruitment of differentiated progeny from self-renewing stem cell populations. Elucidating the genes, cell behaviors and hormonal mechanisms required for stem and progenitor cell renewal and differentiation is therefore important for understanding both human health and many disease syndromes and cancers.

描述（由申请人提供）：这项工作的长期目标是确定脊椎动物后胚胎后发育所需的遗传，细胞和内分泌机制。该提议的重点是斑马鱼的变形，该斑马鱼发生在施肥后12-28天之间，类似于人类胎儿和新生儿发育。在斑马鱼变态过程中发生的许多变化是将胚胎/早期幼虫色素模式转化为成年的幼虫色素，这一过程取决于潜在的干细胞的募集，并且很可能在荷尔蒙对照中。由于甲状腺激素（Th）对于两栖动物的变态以及哺乳动物后的胚胎后发育至关重要。 AIM 1将测试在斑马鱼体细胞和色素模式变形中TH信号传导的作用。这将使用转基因线在整个鱼类或特定的细胞谱系中在特定时间阻止TH信号来实现。为了检查全局内分泌介体如何影响局部细胞的规范和形态发生过程，AIM 2将测试TH信号和WNT信号之间的相互作用，这些信号与颜料细胞的发育以及干细胞自我更新至关重要。这些实验将采用转基因线和其他方法来抑制或刺激这些途径，并测定途径活动和表型结果。最后，可能还有许多其他的迁移后发育中的介体，并且为了识别这些介体，AIM 3将构成未能完全发生变形或在特定性状和细胞类型的变形的突变体的正向遗传筛选。该屏幕将采用破坏基因的载体和转座子介导的插入诱变，从而有效地识别和分析受影响的基因座。这些努力将共同提供有关脊椎动物后胚胎后发展机制的重要新见解。 *脊椎动物在胚胎后阶段经历了广泛的变化，其中许多变化取决于自我更新干细胞种群分化后代的募集。因此，阐明茎和祖细胞更新和分化所需的基因，细胞行为和激素机制对于理解人类健康以及许多疾病综合症和癌症都很重要。