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Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice
Lisa S Andersson1, Martin Larhammar, Fatima Memic
1Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-75124 Uppsala, Sweden.
Nature
|August 31, 2012
Summary
A mutation in the DMRT3 gene alters spinal cord development, significantly impacting mammalian locomotion and gait patterns. This discovery is key to understanding horse breed diversification and spinal circuit control.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
- Animal Locomotion
Background:
- Mammalian locomotion is controlled by complex spinal cord neural networks coordinating limb movements and muscle activation.
- These central pattern-generating networks are established during development and are crucial for producing alternating limb movements and gaits.
- The genetic underpinnings of spinal circuit development and their precise role in locomotion control remain an active area of research.
Purpose of the Study:
- To investigate the functional role of the DMRT3 gene in the development of spinal locomotor networks.
- To determine the impact of a specific DMRT3 gene mutation on locomotion patterns, particularly gaits, in mammals.
- To understand the contribution of DMRT3 to the evolutionary diversification of equine gaits.
Main Methods:
- Genetic analysis of horses with a premature stop codon mutation in the DMRT3 gene.
- Comparative study of wild-type and Dmrt3-null mice to examine DMRT3 expression and function.
- Analysis of spinal cord neuronal populations, specifically the dI6 subdivision, in relation to DMRT3 expression.
Main Results:
- A premature stop codon in the DMRT3 gene significantly alters locomotion patterns in horses, permitting alternate gaits and enhancing harness racing performance.
- Dmrt3 is expressed in dI6 spinal cord neurons and is essential for neuronal specification within this region.
- Dmrt3 plays a critical role in the normal development of coordinated locomotor networks controlling limb movements in mice.
Conclusions:
- DMRT3 is a pivotal gene in configuring spinal circuits that control vertebrate locomotion and stride.
- The identified DMRT3 mutation has profoundly influenced the diversification of domestic horse breeds by altering gait characteristics.
- This research highlights the link between specific gene mutations, neural development, and the evolution of complex behaviors like locomotion.
