De Robertis Edward M, Moriyama Yuki, Colozza Gabriele
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, 90095-1662, USA.
Dev Growth Differ. 2017 Sep;59(7):580-592. doi: 10.1111/dgd.12388. Epub 2017 Aug 16.
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.
博物学家达西·汤普森的经典著作《论生长与形态》于100年前出版。为庆祝这一里程碑，我们展示了非洲爪蟾胚胎实验，这些实验为理解形态发生素梯度的简单定量变化如何影响生物体的进化和形态多样性提供了一个框架。达西·汤普森提出，不同的形态可能是通过改变笛卡尔坐标潜在系统中的物理参数而产生的，该系统在自然界中预先存在，并在进化历史中出现。脊索蛋白是一种由原肠胚背侧的施佩曼组织者分泌的骨形态发生蛋白拮抗剂。脊索蛋白产生了形态发生素梯度，这一观点最早由数学家艾伦·图灵提出。这种背腹（D-V）形态发生素的限速步骤是腹侧的类 tolloid 金属蛋白酶对脊索蛋白的降解。脊索蛋白在原肠胚背侧表达，此处骨形态发生蛋白信号较低，而在相对侧则达到骨形态发生蛋白信号的峰值水平。在鱼类、两栖类、爬行类和鸟类中，腹侧区域的高骨形态发生蛋白信号诱导一种名为 sizzled 的类 tolloid 分泌抑制剂的转录。通过仅在胚胎的腹侧半部分耗尽 sizzled，我们能够在其他方面正常的胚胎中扩展腹后区域。相反，使脊索蛋白稳定的类 tolloid 的腹侧缺失减少了腹侧和尾部结构，模拟了类 tolloid 斑马鱼突变。我们解释了，当一个祖先的反应扩散形态发生素梯度决定形态时，以DNA语言记录的历史限制如何受制于普遍的物理定律。
