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Abstract
The sequential stepping of left and right limbs is a fundamental motor behavior that
underlies walking movements. This relatively simple locomotor behavior is generated
by the rhythmic activity of motor neurons under the control of spinal neural networks
known as central pattern generators (CPGs) that comprise multiple interneuron cell
types. Little, however, is known about the identity and contribution of defined interneuronal
populations to mammalian locomotor behaviors. We show a discrete subset of commissural
spinal interneurons, whose fate is controlled by the activity of the homeobox gene
Dbx1, has a critical role in controlling the left-right alternation of motor neurons
innervating hindlimb muscles. Dbx1 mutant mice lacking these ventral interneurons
exhibit an increased incidence of cobursting between left and right flexor/extensor
motor neurons during drug-induced locomotion. Together, these findings identify Dbx1-dependent
interneurons as key components of the spinal locomotor circuits that control stepping
movements in mammals.