Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement1. These networks produce left–right alternation of limbs as well as coordinated activation of flexor and extensor muscles2. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.
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- Supplementary Information (13.8M)
This file contains Supplementary Figures 1-7, Supplementary Methods, Supplementary Notes, Supplementary References and legends for Supplementary Movies 1-4.
- Supplementary Tables (693K)
This file contains Supplementary Tables 1-6.
- Supplementary Movie 1 (10.1M)
This movie shows a side view of a heterozygous (CA) Swedish Standardbred trotter that performs a fairly symmetric and normal trot stride as well as a very asymmetric stride (see Supplementary Information file for full legend).
- Supplementary Movie 2 (11.5M)
This movie shows a side-by-side view of wild-type and Dmrt3-/- mice (KO) mice during swimming - see Supplementary Information file for full legend.
- Supplementary Movie 3 (35.3M)
This movie shows wild-type and Dmrt3-/- mice during treadmill locomotion - see Supplementary Information file for full legend.
- Supplementary Movie 4 (23.4M)
This movie shows wild-type and Dmrt3-/- mice during airstepping - see Supplementary Information file for full legend.