title: Context-Dependent Gait Choice Elicited by EphA4 Mutation in Lbx1 Spinal Interneurons.
abstract: The most commonly used locomotor strategy in rodents is left-right limb alternation. Mutation of the axon guidance molecule EphA4 profoundly alters this basic locomotor pattern to synchrony. Here we report that conditional mutation of EphA4 in spinal interneurons expressing the transcription factor Lbx1 degrades the robustness in the expression of left-right alternating gait during development. Lbx1 EphA4 conditional mice exhibit alternating gait when walking on ground, but synchronous gait in environments with decreased weight-load, like swimming and airstepping. Using cell-type-specific, transient pharmacogenetic silencing approaches, we attribute this behavioral gait switch to neuronal activity of dorsal Lbx1 spinal interneurons. We also found that in Lbx1 EphA4 conditional mice these dorsal interneurons form aberrant bilateral connections to motor neurons, thereby indirectly transmitting received unilateral proprioceptive sensory information to both spinal sides. Together, our findings reveal the behavioral and circuit-level impact of conditional EphA4 mutation in a transcriptionally defined spinal interneuron subpopulation.
authors.affiliation: Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Satoh
authors.affiliation: Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Christiane
authors.initials: C
authors.lastname: Pudenz
authors.affiliation: Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Electronic address: silvia.arber@unibas.ch.
authors.forename: Silvia
authors.initials: S
authors.lastname: Arber
mesh_terms: D000818:Animals; D001572:Benzofurans; D002772:Cholera Toxin / Q000378:metabolism; D005121:Extremities / Q000502:physiology; D007839:Functional Laterality / Q000235:genetics; D005684:Gait / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000502:physiology*; D008124:Locomotion / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011434:Proprioception / Q000235:genetics; D011804:Quinolines; D036122:Receptor, EphA4 / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology*; D013550:Swimming / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C576715:(3aS,4S,9bS)-N-(2-(8-cyano-1-formyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo(3,2-c)quinolin-4-yl)-2-methylpropyl)-4,6-difluorobenzofuran-2-carboxyamide; D001572:Benzofurans; D006023:Glycoproteins; C491868:Lbx1h protein, mouse; D009124:Muscle Proteins; D011804:Quinolines; D014157:Transcription Factors; D016875:tau Proteins; C062602:transcription factor PTF1; D049452:Green Fluorescent Proteins; D002772:Cholera Toxin; D036122:Receptor, EphA4