Wnt and TGFβ coordinate growth and patterning to regulate size-dependent behaviour
Wnt and TGFβ coordinate growth and patterning to regulate size-dependent behaviour
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DOI：
10.1038/s41586-019-1478-7
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发表时间：
2019-08-29
期刊：
影响因子：
64.8
通讯作者：
Alvarado, Alejandro Sanchez
中科院分区：
文献类型：
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作者：
Arnold, Christopher P.;Benham-Pyle, Blair W.;Alvarado, Alejandro Sanchez
后生动物的生长和模式的差异协调在组织、器官和有机体水平上产生了大小和形状的多样性。虽然组织大小和组织功能可以是相互依赖的（1-5），协调大小和功能的机制仍然知之甚少。Planarians是再生的扁形虫，双向扩展其成年体型（6，7），并通过横向分裂以大小依赖的方式进行无性繁殖（8-10）。这一模式提供了一个强大的背景，以解决差距的知识基础之间的联系大小和功能。在这里，通过生成一个优化的Planarian裂变协议，在Schmidtea mediterranea，我们表明，后代的数量和裂变开始的频率与父母的大小。裂变后代的大小是由以前未识别的机械脆弱的平面沿前后轴以绝对距离沿着固定的。基因的前-后模式的RNA干扰筛选揭示了TGF β和Wnt信号通路的组分作为裂变起始频率的调节剂，而不是裂变平面的位置。最后，生长过程中Wnt和TGF β信号的抑制改变了mechanosensory神经元的模式-一个神经亚群，其根据蠕虫的大小分布并调节裂变行为。我们的研究确定了TGF β和Wnt在调节大小依赖性行为中的作用，并揭示了模式，生长和神经功能之间的相互依赖性。
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.