Sars International Centre for Marine Molecular Biology, University of Bergen, 5006 Bergen, Norway.
Sars International Centre for Marine Molecular Biology, University of Bergen, 5006 Bergen, Norway.
Curr Biol. 2021 Dec 6;31(23):5274-5285.e6. doi: 10.1016/j.cub.2021.09.005. Epub 2021 Sep 28.
Ctenophores are gelatinous marine animals famous for locomotion by ciliary combs. Due to the uncertainties of the phylogenetic placement of ctenophores and the absence of some key bilaterian neuronal genes, it has been hypothesized that their neurons evolved independently. Additionally, recent whole-body, single-cell RNA sequencing (scRNA-seq) analysis failed to identify ctenophore neurons using any of the known neuronal molecular markers. To reveal the molecular machinery of ctenophore neurons, we have characterized the neuropeptide repertoire of the ctenophore Mnemiopsis leidyi. Using the machine learning NeuroPID tool, we predicted 129 new putative neuropeptide precursors. Sixteen of them were localized to the subepithelial nerve net (SNN), sensory aboral organ (AO), and epithelial sensory cells (ESCs), providing evidence that they are neuropeptide precursors. Four of these putative neuropeptides had a behavioral effect and increased the animals' swimming speed. Intriguingly, these putative neuropeptides finally allowed us to identify neuronal cell types in single-cell transcriptomic data and reveal the molecular identity of ctenophore neurons. High-resolution electron microscopy and 3D reconstructions of the nerve net underlying the comb plates confirmed a more than 100-year-old hypothesis of anastomoses between neurites of the same cell in ctenophores and revealed that they occur through a continuous membrane. Our work demonstrates the unique ultrastructure of the peptidergic nerve net and a rich neuropeptide repertoire of ctenophores, supporting the hypothesis that the first nervous system(s) evolved as nets of peptidergic cells.
栉水母是一类著名的以纤毛梳状运动进行运动的海洋动物。由于栉水母的系统发育位置不确定，以及一些关键的两侧神经元基因缺失，因此有人假设它们的神经元是独立进化的。此外，最近的全身单细胞 RNA 测序(scRNA-seq)分析未能使用任何已知的神经元分子标记来识别栉水母神经元。为了揭示栉水母神经元的分子机制，我们对栉水母 Mnemiopsis leidyi 的神经肽谱进行了特征分析。我们使用机器学习 NeuroPID 工具预测了 129 个新的潜在神经肽前体。其中 16 个被定位到上皮下神经网（SNN）、感觉口器（AO）和上皮感觉细胞（ESC），这提供了它们是神经肽前体的证据。其中 4 种潜在的神经肽具有行为效应，能增加动物的游泳速度。有趣的是，这些潜在的神经肽最终使我们能够在单细胞转录组数据中识别神经元细胞类型，并揭示栉水母神经元的分子特征。栉水母栉板下神经网的高分辨率电子显微镜和 3D 重建证实了一个存在了 100 多年的假说，即栉水母同一细胞的神经突之间存在吻合，并揭示了它们是通过连续的膜发生吻合的。我们的工作展示了栉水母肽能神经网的独特超微结构和丰富的神经肽谱，支持了第一个神经系统是作为肽能细胞网络进化而来的假说。
