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

基本信息

批准号：
8208130
负责人：
Sarah Kelly McMenamin
金额：
$ 5.22万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
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

项目摘要

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胚胎后发育所需的遗传、细胞和内分泌机制。该提案重点关注斑马鱼的变态，该变态发生在受精后 12-28 天之间，类似于人类胎儿和新生儿的发育。斑马鱼变态过程中发生的众多变化之一是胚胎/早期幼虫色素模式向成体色素模式的转变，这一过程取决于潜在干细胞的招募，并且可能受到激素控制。甲状腺激素（TH）对于两栖动物变态以及哺乳动物胚胎后发育至关重要。目标 1 将测试 TH 信号在斑马鱼体细胞和色素模式变态中的作用。这将通过使用转基因系在整个鱼或特定细胞谱系中的特定时间阻断 TH 信号来实现。为了研究全局内分泌介质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，已知这些信号对于色素细胞的发育以及干细胞的自我更新至关重要。这些实验将采用转基因系和其他方法来抑制或刺激这些途径并测定途径活性和表型结果。最后，胚胎后发育可能存在许多其他介质，为了识别这些介质，目标 3 将构成对无法完全经历变态或在特定性状和细胞类型的变态中存在缺陷的突变体的正向遗传筛选。该筛选将采用基因破坏载体和转座子介导的插入诱变，从而能够有效识别和分析受影响的位点。这些努力将为脊椎动物胚胎后发育机制提供重要的新见解。 *脊椎动物在胚胎后阶段经历广泛的变化，其中许多变化取决于从自我更新干细胞群中招募分化的后代。因此，阐明干细胞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了解人类健康以及许多疾病综合症和癌症非常重要。