Signaling Architecture Underlying Metamorphic Transitions in Marine Environments

在大多数海滨海洋无脊椎动物中，其生命周期中的一个关键转变是从游动的幼体蜕变为海底栖息的幼体。尽管这一事件在动物生命周期中无处不在，并且在栖息地选择上具有很强的选择性，但对这一过程的机械性理解仍然很差。我的长期目标是了解海胆幼虫发育、变态和定居的调控架构，并获得关于这些过程如何通过内分泌和神经内分泌机制与环境信号整合的新见解。通过利用海胆这一发育生物学和基因调控网络的功能和进化的先进模型，这项研究计划为我们理解动物的胚胎后发育做出了重要贡献。为了实现这一目标，我建立了一个成功的研究项目，研究海胆变态过程中的荷尔蒙和神经递质系统，其结果阐明了环境和生理系统的复杂整合，这些系统共同确保了成功的变态和定居。本提案中所述的工作将继续这项工作。在这五年的授权期内，我的具体目标是1)了解组胺(HA)在海胆变态过程中潜在的调节作用的机制(合成和信号)；2)了解HA信号与一氧化氮(NO)和甲状腺激素(TH)信号的相互作用；3)了解棘球类变态信号结构的演变，特别是HA信号。通过弥合经典幼虫生活史与现代发育、细胞和基因组方法之间的差距，该计划体现了多学科生物学研究的潜力，为动物个体发育、进化和生态学提供了新的见解。

In a majority of sea shore marine invertebrates, a key transition in their life cycles is metamorphosis from a swimming larva to a bottom dwelling juvenile. Despite the ubiquity of this event in animal life cycles and strong selection on habitat choice, a mechanistic understanding of this process remains poor. My long term objective is to understand the regulatory architecture underlying larval development, metamorphosis and settlement in sea urchin larvae and gain novel insights into how these processes are integrated with environmental signals through endocrine and neuroendocrine mechanisms. By using the sea urchin, an advanced model in developmental biology and in the function and evolution of gene regulatory networks, this research program is making essential contributions to our understanding of post-embryonic development in animals. Towards that goal, I have built a successful research program investigating hormonal and neurotransmitter systems in sea urchin metamorphosis, the results of which has elucidated aspects of the complex integration of environmental and physiological systems that conspire to ensure successful metamorphosis and settlement. The work described in this proposal will continue this work. My specific goals for this five-year granting period are to 1) understand the mechanisms (synthesis and signaling) underlying the modulatory function of histamine (HA) in sea urchin metamorphosis; 2) understand the interactions of HA signaling with nitric oxide (NO) and thyroid hormone (TH) signaling; 3) understand the evolution of metamorphic signaling architecture in echinoids with specific emphasis on HA signaling. By bridging the gap between classical larval life history and modern developmental, cellular and genomic approaches, this program exemplifies the potential of multidisciplinary biological research to provide novel insights into animal ontogeny, evolution and ecology.