title: Mirror movement-like defects in startle behavior of zebrafish dcc mutants are caused by aberrant midline guidance of identified descending hindbrain neurons.
abstract: Mirror movements are involuntary movements on one side of the body that occur simultaneously with intentional movements on the contralateral side. Humans with heterozygous mutations in the axon guidance receptor DCC display such mirror movements, where unilateral stimulation results in inappropriate bilateral motor output. Currently, it is unclear whether mirror movements are caused by incomplete midline crossing and reduced commissural connectivity of DCC-dependent descending pathways or by aberrant ectopic ipsilateral axonal projections of normally commissural neurons. Here, we show that in response to unilateral tactile stimuli, zebrafish dcc mutant larvae perform involuntary turns on the inappropriate body side. We show that these mirror movement-like deficits are associated with axonal guidance defects of two identified groups of commissural reticulospinal hindbrain neurons. Moreover, we demonstrate that in dcc mutants, axons of these identified neurons frequently fail to cross the midline and instead project ipsilaterally. Whereas laser ablation of these neurons in wild-type animals does not affect turning movements, their ablation in dcc mutants restores turning movements. Thus, our results demonstrate that in dcc mutants, turns on the inappropriate side of the body are caused by aberrant ipsilateral axonal projections, and suggest that aberrant ipsilateral connectivity of a very small number of descending axons is sufficient to induce incorrect movement patterns.
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania 19104, Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah 84132, and Molecular Medicine Program, University of Utah, Salt Lake City, Utah 84112.
authors.forename: Roshan A
authors.initials: RA
authors.lastname: Jain
authors.forename: Hannah
authors.initials: H
authors.lastname: Bell
authors.forename: Amy
authors.initials: A
authors.lastname: Lim
authors.forename: Chi-Bin
authors.initials: CB
authors.lastname: Chien
authors.forename: Michael
authors.initials: M
authors.lastname: Granato
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D016163:Genes, DCC / Q000235:genetics* / Q000502:physiology*; D005838:Genotype; D007395:Interneurons / Q000502:physiology; D007814:Larva; D009154:Mutation / Q000502:physiology*; D020125:Mutation, Missense / Q000235:genetics / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D013216:Reflex, Startle / Q000502:physiology*; D012249:Rhombencephalon / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013550:Swimming / Q000502:physiology; D014110:Touch / Q000502:physiology; D015027:Zebrafish / Q000502:physiology*
chemical_list: D018076:DNA, Complementary
keywords: DCC; axon guidance; movement disorders; zebrafish