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 Wt1. 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 Wt1 deletion. Locomotion analyses of mice with neuron-specific Wt1 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 Wt1 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 Wt1 mutants was significantly altered. These results show that the development of particular dI6 neurons depends on Wt1 expression and that loss of Wt1 is associated with alterations in locomotion.
Highlights
In vertebrates, rhythmic activity is generated by a network of neurons, commonly referred to as central pattern generators (CPGs) (Jessell, 2000; Grillner, 2003; Kiehn, 2006; Brownstone & Wilson, 2008; Goulding, 2009; Berkowitz et al, 2010)
Until E15.5, embryonic spinal cords showed a constant amount of Wt1+ cells; thereafter, their number gradually decreased until they could no longer be detected in adult mice (Fig 1B)
We have examined Wt1, which marks a subset of dI6 neurons
Summary
Rhythmic activity is generated by a network of neurons, commonly referred to as central pattern generators (CPGs) (Jessell, 2000; Grillner, 2003; Kiehn, 2006; Brownstone & Wilson, 2008; Goulding, 2009; Berkowitz et al, 2010). The locomotor CPGs are located in the spinal cord and consist of distributed networks of interneurons and motor neurons (MNs), which generate an organized motor pattern during repetitive locomotor tasks such as walking and swimming (Grillner, 1985; Kiehn 2006, 2016; Brownstone & Wilson, 2008; McCrea & Rybak, 2008; Goulding, 2009; Grillner & Jessell, 2009). The dI6, V0–V3 interneurons, and MN arise from intermediate or ventral progenitors and are involved in the locomotor circuitry (Goulding, 2009)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
