Integration of endocrine signaling in post-embryonic development via the study of programmed cell death

通过研究程序性细胞死亡将内分泌信号整合到胚胎后发育中

• 批准号: RGPIN-2018-04798
• 负责人: Heyland, Andreas
• 金额: $ 2.91万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757629
• 关键词: Integration; endocrine; signaling; post; embryonic

The long-term goal of my research program is to shed light on the mechanisms regulating larval development and metamorphosis of marine invertebrate larvae. Many marine invertebrate species develop via a bi-phasic life cycle where the embryo transitions into a juvenile via a planktonic larval form. Despite the tremendous diversity of species and larval forms, little information exists on developmental mechanisms regulating this interesting process. My laboratory studies the larvae of the purple sea urchin Strongylocentrotus purpuratus. This species has a fully sequenced genome and represents a model organism for the study of gene regulatory networks in development. Still hormonal (endocrine) regulation of development has received comparatively little attention in this and other marine invertebrate species. Over the past 10 years my laboratory has developed a conceptual framework as well as developmental and physiological tools to study the endocrine regulation of post-embryonic development in this species. Specifically, we are investigating thyroid hormones (THs) and histamine (HA) in larval development and metamorphosis. Here we propose to investigate how TH and HA regulate programmed cell death and how the regulation is linked to higher level environmental input. Our three main objectives are to: 1) Analyze integrin/MAPK mediated TH signaling in skeletogenesis and programmed cell death (PCD); 2) Analyze HA receptor function in PCD during arm retraction and settlement and 3) Integrate HA/TH signaling in the temporal and spatial regulation of PCD during arm retraction and settlement. These three objectives will be addressed by employing a unique combination of functional genomics tools (next generation sequencing, functional knock-downs), physiological experimentation and live imaging, in combination with a diverse array of custom made and commercially available probes. Work from this research will provide novel insights into how endocrine mechanisms regulate post-embryonic development as well as the evolution of endocrine systems in animals.

我的研究计划的长期目标是阐明调节海洋无脊椎动物幼虫发育和变态的机制。许多海洋无脊椎动物物种通过双相生命周期发育，其中胚胎通过浮游幼虫形式过渡到幼年。尽管物种和幼虫形式的巨大多样性，很少有信息存在的发展机制，调节这一有趣的过程。我的实验室研究紫海胆的幼虫。该物种具有完全测序的基因组，是研究发育中基因调控网络的模式生物。然而，激素（内分泌）调节发育在这一物种和其他海洋无脊椎动物物种中受到的关注相对较少。在过去的10年里，我的实验室已经开发了一个概念框架以及发育和生理工具，以研究该物种胚胎后发育的内分泌调节。具体来说，我们正在研究幼虫发育和变态中的甲状腺激素（TH）和组胺（HA）。在这里，我们建议调查TH和HA如何调节程序性细胞死亡，以及如何调节与更高水平的环境输入。我们的三个主要目标是：1）分析整合素/MAPK介导的TH信号在骨骼发育和程序性细胞死亡（PCD）中的作用; 2）分析HA受体在PCD中的作用; 3）整合HA/TH信号在PCD的时间和空间调节中的作用。这三个目标将通过采用功能基因组学工具（下一代测序，功能敲除），生理实验和实时成像的独特组合，结合各种定制和市售探针来解决。这项研究的工作将为内分泌机制如何调节胚胎后发育以及动物内分泌系统的进化提供新的见解。