During evolutionary diversification of vertebrate limbs, the number of toes in even-toed ungulates such as cattle and pigs was reduced and transformed into paired hooves.
Scientists at the University of Basel have identified a gene regulatory switch that was key to evolutionary adaption of limbs in ungulates. The study provides fascinating insights into the molecular history of evolution and is published by Nature today.
The fossil record shows that the first primitive even-toed ungulates had legs with five toes (=digits), just like modern mice and humans. During their evolution, the basic limb skeletal structure was significantly modified such that today’s hippopotami have four toes, while the second and fifth toe face backwards in pigs. In cattle, the distal skeleton consists of two rudimentary dew claws and two symmetrical and elongated middle digits that form the cloven hoof, which provides good traction for walking and running on different terrains.
Comparative analysis of embryonic development
A team led by Prof. Rolf Zeller from the Department of Biomedicine at the University of Basel has now investigated the molecular changes which could be responsible for the evolutionary adaptation of ungulate limbs. To this aim, they compared the activity of genes in mouse and cattle embryos which control the development of fingers and toes during embryonic development.
The development of limbs in both species is initially strikingly similar and molecular differences only become apparent during hand and foot plate development: in mouse embryos the so-called Hox gene transcription factors are distributed asymmetrically in the limb buds which is crucial to the correct patterning of the distal skeleton. In contrast, their distribution becomes symmetrical from early stages onward in limb buds of cattle embryos: “We think this early loss of molecular asymmetry triggered the evolutionary changes that ultimately resulted in development of cloven-hoofed distal limb skeleton in cattle and other even-toed ungulates”, says Developmental Geneticist Prof. Rolf Zeller.
Loss of asymmetry preceded the reduction and loss of digits
The scientists in the Department of Biomedicine then focused their attention on the Sonic Hedgehog (SHH) signaling pathway, as it controls Hox gene expression and the development of five fingers and toes in mice and humans. They discovered that the gene expression in limb buds of cattle embryos is altered, such that the cells giving rise to the distal skeleton fail to express the Hedgehog receptor, called Patched1. Normally, this receptor serves as an antenna for SHH, but without Patched1 the SHH signal cannot be received and the development of five distinct digits is disrupted. The researchers could establish that the altered genomic region – a so-called cis-regulatory module – is linked to the observed loss of Patched1 receptors and digit asymmetry in cattle embryos.
“The identified genetic alterations affecting this regulatory switch offer unprecedented molecular insights into how the limbs of even-toed ungulates diverged from those of other mammals roughly 55 million years ago”, explains Rolf Zeller. At this stage, it is unclear what triggered inactivation of the Patched1 gene regulatory switch. “We assume that it is the result of progressive evolution, as this switch degenerated in cattle and other even-toed ungulates, while it remained fully functional in some vertebrates such as mice and humans”.
Javier Lopez-Rios, Amandine Duchesne, Dario Speziale, Guillaume Andrey, Kevin A. Peterson, Philipp Germann, Erkan Ünal, Jing Liu, Sandrine Floriot, Sarah Barbey, Yves Gallard, Magdalena Müller-Gerbl, Andrew D. Courtney, Christophe Klopp, Sabrina Rodriguez, Robert Ivanek, Christian Beisel, Carol Wicking, Dagmar Iber, Benoit Robert, Andrew P. McMahon, Denis Duboule and Rolf Zeller
Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs
Nature (2014) | doi: 10.1038/nature13289
Prof. Dr. Rolf Zeller, University of Basel, Department of Biomedicine, phone: +41 61 695 30 33, email: email@example.com
http://dx.doi.org/10.1038/nature13289 - Abstract
Reto Caluori | Universität Basel
Single atom alloy platinum-copper catalysts cut costs, boost green technology
09.10.2015 | Tufts University
Controllable protein gates deliver on-demand permeability in artificial nanovesicles
09.10.2015 | Universität Basel
Nondestructive material testing (NDT) is a fast and effective way to analyze the quality of a product during the manufacturing process. Because defective materials can lead to malfunctioning finished products, NDT is an essential quality assurance measure, especially in the manufacture of safety-critical components such as automotive B-pillars. NDT examines the quality without damaging the component or modifying the surface of the material. At this year's Blechexpo trade fair in Stuttgart, Fraunhofer IZFP will have an exhibit that demonstrates the nondestructive testing of high-strength automotive body parts using 3MA. The measurement results are available in a matter of seconds.
To minimize vehicle weight and fuel consumption while providing the highest level of crash safety, automotive bodies are reinforced with elements made from...
The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.
As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...
Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.
Inspired by insects
An interdisciplinary team of researchers has built the first prototype of a miniature particle accelerator that uses terahertz radiation instead of radio...
At present, tiny magnetic whirls – so called skyrmions – are discussed as promising candidates for bits in future robust and compact data storage devices. At...
01.10.2015 | Event News
30.09.2015 | Event News
17.09.2015 | Event News
09.10.2015 | Earth Sciences
09.10.2015 | Life Sciences
09.10.2015 | Life Sciences