Mechanisms of vertebrate post-embryonic developmental progression

脊椎动物胚胎后发育进程的机制

• 批准号: 9440774
• 负责人: Sarah Kelly McMenamin
• 金额: $ 22.66万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9440774
• 关键词: Mechanisms; vertebrate; post; embryonic; developmental

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.

摘要 我们仍然对调节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，了解这些因素的控制， 发育期对于理解成年人的特征是如何形成的至关重要， 在人类胚胎后胎儿和新生儿时期出现的形态缺陷和病症。这 研究利用斑马鱼，它经历了广泛的胚胎后发育， 许多不同器官系统的修饰和成熟;其中许多变化是相似或相同的 人类胚胎发生后发生的过程。该提案采用了几项战略， 了解斑马鱼由幼鱼转变为幼鱼的机制。第一个目标 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定作用， 过渡。多种证据表明甲状腺激素参与了几种发育过程， 过程，但这种激素影响特定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和细胞免疫中的作用。 发育进程和特定的，充分表征的细胞谱系的行为，产生成人 在幼虫向幼鱼过渡期间的色素沉着。第二个目标是采用正向遗传策略， 胚胎后阶段过渡所需的新基因。这种方法已经鉴定出两种突变体艾德 在幼虫发育过程中表现出完全的体细胞停滞， 通常由2周龄和3周龄的野生型幼虫达到。这些表型表明基因受损 是胚胎发育所必需的定位和克隆突变，并表征 它们所属的途径将揭示胚胎后发育过程的基本机制; 该筛选的继续将进一步鉴定幼虫停滞表型。最终目的是利用一个物种相关的 斑马鱼表现出自然的失败，无法执行体细胞后胚胎的终末阶段， 发展主要关注皮肤内的结构和表达，遗传和 发育结构将在胚胎后发育截短的背景下阐明。 这些分析将揭示性状和调控途径之间的脱钩程度，以及是否 休眠的遗传途径保持对胚胎后发育的关键内分泌介质的反应性。 总的来说，这些努力将表征一种已知的内分泌调节因子的形态发生作用， 调节正常胚胎后发育的新因子，并将建立一种新的解剖模型 发育遗传途径和内分泌机制的进化方式。而且这 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 人口生态学，并将建立她的独立研究实验室的基础。