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Wnt and TGFβ coordinate growth and patterning to regulate size-dependent behaviour

机译:Wnt和TGFβ协调生长和模式调控大小依赖性行为

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摘要

Differential coordination of growth and patterning across metazoans gives rise to a diversity of sizes and shapes at tissue, organ and organismal levels. Although tissue size and tissue function can be interdependent(1-5), mechanisms that coordinate size and function remain poorly understood. Planarians are regenerative flatworms that bidirectionally scale their adult body size(6,7) and reproduce asexually, via transverse fission, in a size-dependent manner(8-10). This model offers a robust context to address the gap in knowledge that underlies the link between size and function. Here, by generating an optimized planarian fission protocol in Schmidtea mediterranea, we show that progeny number and the frequency of fission initiation are correlated with parent size. Fission progeny size is fixed by previously unidentified mechanically vulnerable planes spaced at an absolute distance along the anterior-posterior axis. An RNA interference screen of genes for anterior-posterior patterning uncovered components of the TGF beta and Wnt signalling pathways as regulators of the frequency of fission initiation rather than the position of fission planes. Finally, inhibition of Wnt and TGF beta signalling during growth altered the patterning of mechanosensory neurons-a neural subpopulation that is distributed in accordance with worm size and modulates fission behaviour. Our study identifies a role for TGF beta and Wnt in regulating size-dependent behaviour, and uncovers an interdependence between patterning, growth and neurological function.
机译:跨后生动物的生长和模式差异协调导致组织,器官和机体水平的大小和形状多样化。尽管组织的大小和功能可以相互依赖(1-5),但协调大小和功能的机制仍知之甚少。扁平人是一种可再生的扁虫,可以双向缩放其成年体的大小(6,7),并通过横向裂变以大小依赖的方式无性繁殖(8-10)。该模型提供了一个强大的上下文,可以解决规模与功能之间联系的基础知识鸿沟。在这里,通过在Schmidtea mediterranea中生成一个优化的涡旋裂变协议,我们表明后代数量和裂变起始的频率与亲代大小相关。裂变后代的大小由沿前-后轴以绝对距离隔开的先前未确定的机械脆弱平面固定。用于前后图案化的基因的RNA干扰筛查未发现的TGFβ和Wnt信号通路成分,它们是裂变起始频率而非裂变平面位置的调节剂。最后,在生长过程中对Wnt和TGFβ信号的抑制改变了机械感觉神经元的模式-一种根据蠕虫大小分布并调节裂变行为的神经亚群。我们的研究确定了TGFβ和Wnt在调节大小依赖性行为中的作用,并揭示了图案形成,生长和神经功能之间的相互依赖性。

著录项

  • 来源
    《Nature》 |2019年第7771期|655-659|共5页
  • 作者单位

    Stowers Inst Med Res, Kansas City, MO 64110 USA|Howard Hughes Inst Med Res, Kansas City, MO 64110 USA;

    Stowers Inst Med Res, Kansas City, MO 64110 USA;

    Stowers Inst Med Res, Kansas City, MO 64110 USA;

    Stowers Inst Med Res, Kansas City, MO 64110 USA;

    Stowers Inst Med Res, Kansas City, MO 64110 USA|Howard Hughes Inst Med Res, Kansas City, MO 64110 USA;

  • 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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  • 正文语种 eng
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