从文昌鱼胰岛素样多肽（ILP）基因功能探讨脊椎动物胰岛素/IGF通路的进化

解析重要代谢通路的功能形成和演化过程是进化发育生物学和动物学研究的热点和核心内容。脊椎动物胰岛素/胰岛素样生长因子（IGF）调控通路控制代谢，生长和衰老等重要生理过程。相比无脊椎动物，脊椎动物胰岛素/IGF通路拥有更多信号类型，更多信号-受体组合，以及更精细的调控系统；但我们不清楚脊椎动物这种复杂信号通路起源和进化的过程。文昌鱼是现存脊椎动物近亲，其基因组较小且诸多通路具备与脊椎动物中通路类似的雏形，是研究脊椎动物进化的理想动物模型。本项目拟采用文昌鱼作为研究对象，在前期工作的基础上利用CRISPR/Cas9基因编辑技术和比较转录组学等方法深入研究文昌鱼胰岛素家族基因以及胰岛素/IGF通路的主要构成元件和功能，阐释胰岛素/IGF信号通路在脊椎生物早期的进化过程。

The vertebrate insulin/insulin-like growth factor (IGF) pathway is an essential regulatory pathway controlling dietary metabolism, growth, and the aging process. Although insulin-like peptides (ILP) have been identified in multiple Bilaterian lineages, vertebrates are unique in the sense that they have a complex combination of signal peptides, signal receptors, and multiple levels of signal regulation. Given limited evidence on ILP presence in other animal lineages, especially other deuterostomes, the origins and evolution of the vertebrate insulin/IGF pathway remain unknown. Cephalochordates are considered to be one of the closest relatives to vertebrates and are ideal animal models used to study vertebrate evolution given their relatively small genome size and simple body plan. In this proposal, the applicant uses the Florida lancelet (Branchiostoma floridae, referred to as amphioxus) as an animal model to explore the evolutionary origins of the vertebrate insulin/IGF pathway. Based on existing work, this proposal aims to use a combination of CRISPR/Cas9 gene editing and comparative transcriptomics to characterize the function of amphioxus BfIlp1 and identify critical implications of amphioxus insulin/IGF pathway genes on development and dietary metabolism. Through comparisons between the amphioxus and vertebrate insulin/IGF pathways, this proposal aims to provide new insights evolution of the vertebrate insulin/IGF pathway.