Generation of animal form by the Chordin/Tolloid/BMP gradient: 100 years after D'Arcy Thompson

• Published in: Development, growth & differentiation Vol. 59; no. 7; pp. 580 - 592
• Main Authors: De Robertis, Edward M., Moriyama, Yuki, Colozza, Gabriele
• Format: Journal Article
• Language: English
• Published: Japan 01.09.2017
• Subjects: Animals; Bone Morphogenetic Proteins - metabolism; dorsal‐ventral patterning; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; evolution of body form; Glycoproteins - metabolism; Intercellular Signaling Peptides and Proteins - metabolism; Models, Biological; morphogen gradient; morphogenesis; reaction‐diffusion; Signal Transduction - physiology; Tolloid-Like Metalloproteinases - metabolism; Xenopus laevis; evolution of body form; reaction-diffusion; morphogenesis; morphogen gradient; dorsal-ventral patterning
• ISSN: 0012-1592; 1440-169X; 1440-169X
• DOI: 10.1111/dgd.12388

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. We present experiments in which the form of the Xenopus embryo is modified by depleting the chordinase Tolloid or its inhibitor Sizzled specifically in ventral cells. This changes body form in ways reminiscent of D'Arcy Thompson's proposals in his 1917 book “On Growth and Form”.