Adapting the pantograph limb: Differential robustness of fore- and hindlimb kinematics against genetically induced perturbation in the neural control networks and its evolutionary implications.

The evolutionary transformation of limb morphology to the four-segmented pantograph of therians is among the milestones of mammalian evolution. But, it is still unknown if changes of the mechanical limb function were accompanied by corresponding changes in development and sensorimotor control. The impressive locomotor performance of mammals leaves no doubt about the high integration of pattern formation, neural control and mechanics. But, deviations from normal intra- and interlimb coordination (spatial and temporal) become evident in the presence of perturbations. We induced a perturbation in the development of the neural circuits of the spinal cord of mice (Mus musculus) using a deletion of the Wilms tumor suppressor gene Wt1 in a subpopulation of dI6 interneurons. These interneurons are assumed to participate in the intermuscular coordination within the limb and in left-right-coordination between the limbs. We describe the locomotor kinematics in mice with conditional Wt1 knockout and compare them to mice without Wt1 deletion. Unlike knockout neonates, knockout adult mice do not display severe deviations from normal (=control group) interlimb coordination, but the coordinated protraction and retraction of the limbs is altered. The forelimbs are more affected by deviations from the control than the hindlimbs. This observation appears to reflect a different degree of integration and resistance against the induced perturbation between the limbs. Interestingly, the observed effects are similar to locomotor deficits reported to arise when sensory feedback from proprioceptors or cutaneous receptors is impaired. A putative participation of Wt1 positive dI6 interneurons in sensorimotor integration is therefore considered.