Generation of animal form by the Chordin/Tolloid/BMP gradient: 100 years after D'Arcy Thompson
Generation of animal form by the Chordin/Tolloid/BMP gradient: 100 years after D'Arcy Thompson
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DOI：
10.1111/dgd.12388
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发表时间：
2017-09-01
影响因子：
2.5
通讯作者：
Colozza, Gabriele
中科院分区：
文献类型：
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作者：
De Robertis, Edward M.;Moriyama, Yuki;Colozza, Gabriele
博物学家达西·汤普森的经典著作《论生长与形态》出版于100年前。为了庆祝这一里程碑，我们提供了非洲爪哇胚胎的实验，这些实验提供了一个框架，可以理解形态生成梯度的简单、定量转换可能如何影响生物体的进化和形态多样性。达西·汤普森提出，可以通过修改笛卡尔坐标系中的物理参数来产生不同的形态，笛卡尔坐标系是自然界中预先存在的，并在进化史上出现。Chordin是一种BMP拮抗剂，由位于原肠胚背侧的Spemann组织者分泌。正如数学家艾伦·图灵最先提出的那样，Chordin产生形态梯度。这种背侧-腹侧(D-V)形态原的限速步骤是腹侧Tolloid金属蛋白酶对Chordin的降解。Chordin在BMP信号较低的背侧原肠胚处表达，而在对侧达到BMP信号的峰值。在鱼类、两栖动物、爬行动物和鸟类中，腹侧区域的高BMP信号诱导一种名为sizzed的Tolloid分泌抑制物的转录。通过消耗仅在胚胎腹侧一半发出的嘶嘶声，我们能够在其他情况下正常的胚胎中扩大腹后区。相反，腹侧Tolloid的耗尽，稳定了Chordin，减少了腹侧和尾部结构，表现出Tolloid斑马鱼的突变。我们解释了当祖先的反应-扩散形态梯度决定形成时，记录在DNA语言中的历史约束如何成为普遍物理定律的制约。
The classic book "On Growth and Form" by naturalist D'Arcy Thompson was published 100 years ago. To celebrate this landmark, we present experiments in the Xenopus embryo that provide a framework for understanding how simple, quantitative transformations of a morphogen gradient might have affected evolution and morphological diversity of organisms. D'Arcy Thompson proposed that different morphologies might be generated by modifying physical parameters in an underlying system of Cartesian coordinates that pre-existed in Nature and arose during evolutionary history. Chordin is a BMP antagonist secreted by the Spemann organizer located on the dorsal side of the gastrula. Chordin generates a morphogen gradient as first proposed by mathematician Alan Turing. The rate-limiting step of this dorsal-ventral (D-V) morphogen is the degradation of Chordin by the Tolloid metalloproteinase in the ventral side. Chordin is expressed at gastrula on the dorsal side where BMP signaling is low, while at the opposite side peak levels of BMP signaling are reached. In fishes, amphibians, reptiles and birds, high BMP signaling in the ventral region induces transcription of a secreted inhibitor of Tolloid called Sizzled. By depleting Sizzled exclusively in the ventral half of the embryo we were able to expand the ventro-posterior region in an otherwise normal embryo. Conversely, ventral depletion of Tolloid, which stabilizes Chordin, decreased ventral and tail structures, phenocopying the tolloid zebrafish mutation. We explain how historical constraints recorded in the language of DNA become subject to the universal laws of physics when an ancestral reaction-diffusion morphogen gradient dictates form.