Neuron-specific inactivation of <i>Wt1</i> alters locomotion in mice and changes interneuron composition in the spinal cord

Abstract

Locomotion is coordinated by neuronal circuits of the spinal cord. Recently, dI6 neurons were shown to participate in the control of locomotion. A subpopulation of dI6 neurons expresses the Wilms tumor suppressor gene <i>Wt1</i>. However, the function of Wt1 in these cells is not understood. Here, we aimed to identify behavioral changes and cellular alterations in the spinal cord associated with <i>Wt1</i> deletion. Locomotion analyses of mice with neuron-specific <i>Wt1</i> deletion revealed a slower walk with a decreased stride frequency and an increased stride length. These mice showed changes in their fore-/hindlimb coordination, which were accompanied by a loss of contralateral projections in the spinal cord. Neonates with <i>Wt1</i> deletion displayed an increase in uncoordinated hindlimb movements and their motor neuron output was arrhythmic with a decreased frequency. The population size of dI6, V0, and V2a neurons in the developing spinal cord of conditional <i>Wt1</i> mutants was significantly altered. These results show that the development of particular dI6 neurons depends on <i>Wt1</i> expression and that loss of <i>Wt1</i> is associated with alterations in locomotion.