TY - JOUR T1 - Loss of Wt1 in the murine spinal cord alters interneuron composition and locomotion JF - bioRxiv DO - 10.1101/226316 SP - 226316 AU - Danny Schnerwitzki AU - Sharn Perry AU - Anna Ivanova AU - Fabio Viegas Caixeta AU - Paul Cramer AU - Sven Günther AU - Kathrin Weber AU - Atieh Tafreshiha AU - Lore Becker AU - Ingrid L. Vargas Panesso AU - Thomas Klopstock AU - Martin Hrabe de Angelis AU - Manuela Schmidt AU - Klas Kullander AU - Christoph Englert Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/11/29/226316.abstract N2 - Rhythmic and patterned locomotion is driven by spinal cord neurons that form neuronal circuits, referred to as central pattern generators (CPGs). Recently, dI6 neurons were suggested to participate in the control of locomotion. The dI6 neurons can be subdivided into three populations, one of which expresses the Wilms tumor suppressor gene Wt1. However, the role that Wt1 exerts on 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 that these mice ran slower than controls 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 loss of Wt1 is associated with alterations in locomotion. ER -