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
Understanding a missing link in how antidepressants work
25.11.2015 | Max Planck Institute of Psychiatry, München
Plant Defense as a Biotech Tool
25.11.2015 | Austrian Centre of Industrial Biotechnology (ACIB)
The Fraunhofer Institute for Solar Energy Systems ISE has installed 70 photovoltaic modules on the outer façade of one of its lab buildings. The modules were...
Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.
In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...
In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.
Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...
Researchers at Heidelberg University have devised a new way to study the phenomenon of magnetism. Using ultracold atoms at near absolute zero, they prepared a...
AWI researchers’ unique 15-year observation series reveals how sensitive marine ecosystems in polar regions are to change
The warming of arctic waters in the wake of climate change is likely to produce radical changes in the marine habitats of the High North. This is indicated by...
25.11.2015 | Event News
17.11.2015 | Event News
21.10.2015 | Event News
25.11.2015 | Agricultural and Forestry Science
25.11.2015 | Earth Sciences
25.11.2015 | Physics and Astronomy