Over the course of this summer's Olympics, the full spectrum of human gaits has been on display, from Ding Chen's wiggly high speed walk to Mo Farrah's effortless lope and Usain Bolt's powerful sprint. All animals have evolved a spectrum of locomotion patterns, or gaits, in order to maximise their efficiency at different speeds. However, we know very little about how these different motor patterns are selected within the nervous system.
All horses have at least three gaits: walking, trotting and galloping, in order of increasing speed. However, some – including harness-racing horses and some Icelandic breeds – have gained additional gaits such as pacing, in which the two legs on one side of the body are moved in unison. What allows these animals to move differently from the rest? A collaborative study by teams in Sweden, Iceland and the USA, recently published in Nature, sheds light on this phenomenon by focusing on the genetic differences between various horse breeds with different numbers of gaits.
By comparing the genomes of hundreds of horses of various different breeds, they found that nearly all animals that have an additional gait (‘gaited’ horses) carry two copies of a mutation in a transcription factor gene, DMRT3. This mutation, which is never found in ‘non-gaited’ animals, results in the production of a truncated version of the transcription factor protein that presumably does not function normally, and allows the horse to perform additional gaits. How does the mutation lead to this ability?
The authors reasoned they would be better off looking at mice to address this question: the neurons that underlie their locomotion have been carefully described and can be experimented on with relative ease. Mice that lack DMRT3 altogether have largely normal motor coordination, but have problems running at high speeds. Electrophysiological recordings from their spinal cords showed that the neural circuit that is responsible for generating rhythmic muscle contractions during locomotion is disturbed, firing largely uncoordinated bursts of action potentials. This suggests that DMRT3 is required in mice for either the generation or the continued function of the circuitry that produces coordinated movements. The researchers needed to know more about the identity of the DMRT3-expressing cells in order to understand what might be going on.
Using different labelling techniques, the authors found that these cells make connections between the left and right halves of the spinal cord, and that they have an inhibitory function. In DMRT3 mutants, the identity of these cells is altered, resulting in fewer connections between the left and right sides of the spinal cord being made. These results are consistent with the idea that DMRT3 is necessary for the coordination between limbs, although the exact role of the DMRT3-expressing neurons remains unclear.
This study has identified a gene that plays an interesting role in determining how different modes of locomotion are generated. It is involved in the ability to produce alternative gaits, possibly by regulating the development of the circuitry in the spinal cord that generates these movements. It will be very interesting to see how the neurons that express this gene interact with the rest of the locomotor network in order to coordinate gait.
