美国斯托尔斯医学研究所Alejandro Sanchez Alvarado研究团队发现,Wnt和TGFβ通过协调生长和模式化来调节个体大小相关的生物行为。这一研究成果发表在2019年8月29日出版的《自然》上。
通过在Schmidtea mediterranea(一种涡虫)中建立优化的横裂生殖实验方案,研究人员发现子代数和起始频率与亲本大小相关。横裂子代大小被沿着前-后轴的绝对距离的机械力脆弱平面所固定,这是以前不知道的。RNA干扰筛选出用于前-后轴模式化的基因,并揭示了TGFβ和Wnt信号途径的组分,其调节横裂的起始频率而不是横裂平面的位置。最后,生长期间对Wnt和TGFβ信号的抑制改变了机械感觉神经元的模式,这是一种神经亚群,其根据涡虫大小分布并调节横裂行为。这项研究确定了TGFβ和Wnt在调节大小依赖性行为中的作用,并揭示了模式化、生长和神经功能之间的相互依赖性。
据悉,多细胞生物的生长和模式化的差异性协调在组织、器官和生物体水平上产生大小和形状的多样性。尽管组织的大小和功能可以相互依赖,但协调大小和功能的机制仍然知之甚少。涡虫是可再生的扁虫,它们双向地扩大其成体的个体大小,并可通过横裂生殖以尺寸依赖的方式进行无性繁殖。这个模型提供了一个强有力的背景,来解决大小与功能之间联系的问题。
附:英文原文
Title: Wnt and TGFβ coordinate growth and patterning to regulate size-dependent behaviour
Author: Christopher P. Arnold, Blair W. Benham-Pyle, Jeffrey J. Lange, Christopher J. Wood, Alejandro Snchez Alvarado
Issue&Volume: Volume 572 Issue 7771
Abstract: 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 interdependent1,2,3,4,5, mechanisms that coordinate size and function remain poorly understood. Planarians are regenerative flatworms that bidirectionally scale their adult body size6,7 and reproduce asexually, via transverse fission, in a size-dependent manner8,9,10. 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 TGFβ and Wnt signalling pathways as regulators of the frequency of fission initiation rather than the position of fission planes. Finally, inhibition of Wnt and TGFβ 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 TGFβ and Wnt in regulating size-dependent behaviour, and uncovers an interdependence between patterning, growth and neurological function.
DOI: 10.1038/s41586-019-1478-7
Source:https://www.nature.com/articles/s41586-019-1478-7
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html