Mechanisms of vertebrate post-embryonic developmental progression

摘要 我们仍然对调控和同步形态发生事件的机制知之甚少 脊椎动物发育的后期阶段。尽管如此，了解控制这些的因素之后 发育阶段对于理解成人特征是如何形成的是必不可少的，并将有助于深入了解 在人类胚胎后、胎儿和新生儿时期出现的形态缺陷和紊乱。这 研究利用斑马fish，它经历了广泛的胚胎后发育，包括 Modifi阳离子在许多不同器官系统中的成熟；这些变化中的许多是相似或相同的 到人类胚胎发生后发生的过程。这项建议采用了几种策略来实现 了解斑马fish从幼虫向幼虫转化的机制。fi的首要目标 采用有针对性的方法，测试甲状腺激素在胚胎后发育中的特殊fic作用。 过渡。多条证据表明，甲状腺激素参与了几种发育过程 斑马fish中的过程，但这种激素影响特定的fic形态发生过程和细胞的能力。 行为仍不清楚。这一目标将测试甲状腺激素在促进全球体细胞 发育进程和一种特定的fic的行为，这是一种特征良好的产生成虫的细胞谱系 幼虫向幼鱼转变过程中的色素沉着。第二个目标是采用一种前向遗传策略来识别 胚胎后阶段转变所需的新基因。这种方法已经识别了fi的两个突变体 在幼虫发育期间表现出完全的体细胞停滞，在不同的阶段停止个体发育 通常由2周和3周大的野生型幼虫到达。这些表型表明基因受损。 对于胚胎后发育来说是绝对必要的。对突变进行定位和克隆，并对其进行特征分析 它们所属的途径将揭示胚胎后发育过程所必需的机制； 继续这一筛选将确定更多的幼虫滞留表型。fiNal的目标是利用一个与之相关的物种 对斑马fish表现出一种天然的不能执行体细胞后胚胎后期的阶段 发展。主要关注皮肤内的结构和表达，遗传和 发育架构将在胚胎后发育截断的背景下阐明。 这些分析将揭示特征和调控途径之间的脱钩程度，以及 休眠的遗传途径保持了对胚胎后发育的关键内分泌调节因子的反应性。 总体而言，这些努力将表征已知的内分泌调节因子的形态发生作用，将确定 调节正常胚胎后发育的新因素，并将建立一个新的解剖模型 发育遗传途径和内分泌机制可以进化的方式。此外，这一点 该项目将完成一名具有以下背景的学者的发育生物学和遗传学培训 种群生态学，并将为她的独立研究实验室奠定基础。

ABSTRACT We still know very little about the mechanisms that regulate and synchronize morphogenetic events during later stages of vertebrate development. Nonetheless, understanding the factors controlling these later developmental periods is essential to understanding how adult traits form, and will lend insight into morphological defects and disorders that arise during human post-embryonic fetal and neonatal periods. This research utilizes the zebrafish, which undergoes extensive post-embryonic development involving modifications and maturation in many different organ systems; many of these changes are similar or identical to processes that occur following embryogenesis in humans. This proposal employs several strategies towards understanding the mechanisms underlying the zebrafish transformation from larva to juvenile. The first aim adopts a targeted approach, testing the specific roles of thyroid hormone in post-embryonic developmental transitions. Multiple lines of evidence indicate that thyroid hormone is involved in several developmental processes in zebrafish, but the ability of this hormone to effect specific morphogenetic processes and cellular behaviors remains unclear. This aim will test roles of thyroid hormone in promoting both global somatic developmental progression and the behaviors of a specific, well-characterized cell lineage that produces adult pigmentation during the larval-to-juvenile transition. The second aim takes a forward genetic strategy to identify novel genes required for post-embryonic stage transitions. This approach has already identified two mutants that exhibit complete somatic arrest during larval development, ceasing ontogenetic progression at stages normally reached by 2- and 3-week old wild-type larvae. These phenotypes suggest an impairment of genes absolutely required for post-embryonic progression. Mapping and cloning the mutations and characterizing the pathways to which they belong will reveal mechanisms essential for post-embryonic developmental processes; continuation of this screen will identify further larval arrest phenotypes. The final aim utilizes a species related to zebrafish that exhibits a natural failure to execute the terminal stages of somatic post-embryonic development. Focusing primarily on the structure and expression within the skin, changes in genetic and developmental architecture will be elucidated in this context of post-embryonic developmental truncation. These analyses will reveal the both extent of decoupling between traits and regulatory pathways, and whether dormant genetic pathways retain responsiveness to a key endocrine mediator of post-embryonic development. Overall, these efforts will characterize the morphogenetic roles of a known endocrine regulator, will identify novel factors that regulate normal post-embryonic progression, and will establish a novel model for dissecting the ways in which developmental genetic pathways and endocrine mechanisms can evolve. Moreover, this project will complete the developmental biology and genetics training of a scholar with a background in population ecology, and will establish establish the foundation for her independent research laboratory.