Posted by: Pamela Mason1 JUL 2014
During evolutionary diversification of vertebrate limbs, the number of toes in even-toed hoofed animals 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 these animals. The fossil record shows that the first primitive even-toed hoofed animals had legs with five digits like mice and humans but during their evolution, the basic limb skeletal structure was modified such that for example 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.
Interested in the molecular changes that could be responsible for the evolutionary adaptation of limbs in hoofed animals, the Basel researchers compared the activity of genes in mouse and cattle embryos that control the development of fingers and toes during embryonic development. They found that the development of limbs in both species is initially strikingly similar and molecular differences only become apparent during hand and footplate 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, in cattle embryos, the distribution of the gene transcription factors in the limb buds becomes symmetrical from early stages onward. Hox gene expression and the development of five fingers and toes in mice and humans are under the control of the so-called sonic hedgehog (SHH) signalling pathway.
The researchers also discovered that in the limb buds of cattle embryos, the cells giving rise to the distal skeleton fail to express the SHH receptor and hence the development of five digits is disrupted. The suggestion is that these genetic alterations offer insight into how the limbs of even toed hoofed animals like cattle diverged from that of other animals roughly 55 million years ago.