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Specialized filopodia direct long-range transport of SHH during vertebrate tissue patterning

机译：专门的丝足病在脊椎动物组织构图过程中直接SHH的远距离运输

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摘要

The ability of signalling proteins to traverse tissues containing tightly packed cells is of fundamental importance for cell specification and tissue development; however, how this is achieved at a cellular level remains poorly understood. For more than a century, the vertebrate limb bud has served as a model for studying cell signalling during embryonic development. Here we optimize single-cell realtime imaging to delineate the cellular mechanisms for how signalling proteins, such as sonic hedgehog (SHH), that possess membrane-bound covalent lipid modifications traverse long distances within the vertebrate limb bud in vivo. By directly imaging SHH ligand production under native regulatory control in chick (Gallus gallus) embryos, our findings show that SHH is unexpectedly produced in the form of a particle that remains associated with the cell via long cytoplasmic extensions that span several cell diameters. We show that these cellular extensions are a specialized class of actin-based filopodia with novel cytoskeletal features that have not been previously described. Notably, particles containing SHH travel along these extensions with a net anterograde movement within the field of SHH cell signalling. We further show that in SHH-responding cells, specific subsets of SHH co-receptors, including cell adhesion molecule downregulated by oncogenes (CDO) and brother of CDO (BOC), actively distribute and co-localize in specific micro-domains within filopodial extensions, far from the cell body. Stabilized interactions are formed between filopodia containing SHH ligand and those containing co-receptors over a long range. These results suggest that contact-mediated release propagated by specialized filopodia contributes to the delivery of SHH at a distance. Together, these studies identify an important mode of communication between cells that considerably extends our understanding of ligand movement and reception during vertebrate tissue patterning.
机译：信号蛋白穿越包含紧密堆积细胞的组织的能力对于细胞规格和组织发育至关重要。然而，如何在细胞水平上实现这一点仍然知之甚少。一个多世纪以来，脊椎动物肢芽一直是研究胚胎发育过程中细胞信号传导的模型。在这里，我们优化了单细胞实时成像，以描述具有膜结合共价脂质修饰的信号蛋白（如声波刺猬（SHH））如何在体内脊椎动物肢芽内长距离穿越的细胞机制。通过直接成像在鸡（鸡）胚胎的天然调节控制下的SHH配体产生，我们的发现表明，SHH出人意料地以颗粒的形式产生，该颗粒通过跨越多个细胞直径的长胞质延伸与细胞保持结合。我们显示这些细胞扩展是一类特殊的基于肌动蛋白的丝状伪足，具有先前未描述的新型细胞骨架特征。值得注意的是，含有SHH的颗粒在SHH细胞信号传导区域内以净顺行运动沿着这些延伸行进。我们进一步表明，在SHH反应细胞中，SHH共受体的特定子集，包括由癌基因（CDO）和CDO的兄弟（BOC）下调的细胞粘附分子，活跃地分布和共定位在丝虫延伸的特定微区中，远离细胞体。含有SHH配体的丝状伪足与含有共受体的丝状伪足之间形成了稳定的相互作用。这些结果表明，由专门丝状伪足传播的接触介导的释放有助于远距离输送SHH。总之，这些研究确定了细胞之间重要的通讯方式，大大扩展了我们对脊椎动物组织构图过程中配体运动和接收的理解。

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  • 来源
    《Nature》 |2013年第7451期|628-632|共5页
  • 作者

    Timothy A. Sanders; Esther Llagostera; Maria Barna;

  • 作者单位

    Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California 94158, USA,Department of Pediatrics, Division of Neonatology, University of California San Francisco, San Francisco, California 94158, USA;

    Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California 94158, USA,Department of Developmental Biology, Stanford University, Stanford, California 94305, USA,Department of Genetics, Stanford University, Stanford;

    Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California 94158, USA,Department of Developmental Biology, Stanford University, Stanford, California 94305, USA,Department of Genetics, Stanford University, Stanford;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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