RT Journal Article SR Electronic T1 Loss of Wt1 in the murine spinal cord alters interneuron composition and locomotion JF bioRxiv FD Cold Spring Harbor Laboratory SP 226316 DO 10.1101/226316 A1 Danny Schnerwitzki A1 Sharn Perry A1 Anna Ivanova A1 Fabio Viegas Caixeta A1 Paul Cramer A1 Sven Günther A1 Kathrin Weber A1 Atieh Tafreshiha A1 Lore Becker A1 Ingrid L. Vargas Panesso A1 Thomas Klopstock A1 Martin Hrabe de Angelis A1 Manuela Schmidt A1 Klas Kullander A1 Christoph Englert YR 2017 UL http://biorxiv.org/content/early/2017/11/29/226316.abstract AB 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.