英国埃克塞特大学Steffen Scholpp研究组揭示斑马鱼细胞导管介导的活性Wnt5b-Ror2复合物运输。2023年12月20日，《自然》杂志在线发表了这项成果。

研究人员表示，化学信号是胚胎中细胞交流的主要方式。其基本原理是指一组产生配体的细胞和一组因表达相应受体而对该信号做出反应的细胞。在斑马鱼胚胎中，Wnt5b与受体Ror2结合，触发Wnt-平面细胞极性（PCP）信号通路，调节组织极性和细胞迁移。然而，目前仍不清楚这种亲脂性配体是如何从源细胞通过细胞外水空间转运到靶组织的。

研究人员提供的证据表明，Wnt5b和Ror2一起被装载在称为细胞导管的长突起上。研究人员的数据进一步表明，活性Wnt5b-Ror2复合物在产生细胞内形成，并从这些细胞核转移到接收细胞。然后，无论Ror2受体的功能状态如何，接收细胞都有能力启动Wnt-PCP信号。在组织水平上，研究人员进一步表明，依赖细胞因子的活性Wnt5b-Ror2扩散会影响斑马鱼原肠胚的聚合和延伸。研究人员认为，细胞因子介导的配体-受体复合物转移是旁分泌信号的重要机制。这可能会促使人们重新评估仅根据受体的表达来描述有反应和无反应组织的传统概念。

附：英文原文

Title: Cytoneme-mediated transport of active Wnt5b–Ror2 complexes in zebrafish

Author: Zhang, Chengting, Brunt, Lucy, Ono, Yosuke, Rogers, Sally, Scholpp, Steffen

Issue&Volume: 2023-12-20

Abstract: Chemical signalling is the primary means by which cells communicate in the embryo. The underlying principle refers to a group of ligand-producing cells and a group of cells that respond to this signal because they express the appropriate receptors1,2. In the zebrafish embryo, Wnt5b binds to the receptor Ror2 to trigger the Wnt–planar cell polarity (PCP) signalling pathway to regulate tissue polarity and cell migration3,4. However, it remains unclear how this lipophilic ligand is transported from the source cells through the aqueous extracellular space to the target tissue. In this study, we provide evidence that Wnt5b, together with Ror2, is loaded on long protrusions called cytonemes. Our data further suggest that the active Wnt5b–Ror2 complexes form in the producing cell and are handed over from these cytonemes to the receiving cell. Then, the receiving cell has the capacity to initiate Wnt–PCP signalling, irrespective of its functional Ror2 receptor status. On the tissue level, we further show that cytoneme-dependent spreading of active Wnt5b–Ror2 affects convergence and extension in the zebrafish gastrula. We suggest that cytoneme-mediated transfer of ligand–receptor complexes is a vital mechanism for paracrine signalling. This may prompt a reevaluation of the conventional concept of characterizing responsive and non-responsive tissues solely on the basis of the expression of receptors.

DOI: 10.1038/s41586-023-06850-7

Source: https://www.nature.com/articles/s41586-023-06850-7