title: The zebrafish amyloid precursor protein-b is required for motor neuron guidance and synapse formation.
abstract: The amyloid precursor protein (APP) is a transmembrane protein mostly recognized for its association with Alzheimer's disease. The physiological function of APP is still not completely understood much because of the redundancy between genes in the APP family. In this study we have used zebrafish to study the physiological function of the zebrafish APP homologue, appb, during development. We show that appb is expressed in post-mitotic neurons in the spinal cord. Knockdown of appb by 50-60% results in a behavioral phenotype with increased spontaneous coiling and prolonged touch-induced activity. The spinal cord motor neurons in these embryos show defective formation and axonal outgrowth patterning. Reduction in Appb also results in patterning defects and changed density of pre- and post-synapses in the neuromuscular junctions. Together, our data show that development of functional locomotion in zebrafish depends on a critical role of Appb in the patterning of motor neurons and neuromuscular junctions.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, S-41345 Gothenburg, Sweden. alexandra.abramsson@neuro.gu.se
authors.forename: Alexandra
authors.initials: A
authors.lastname: Abramsson
authors.forename: Petronella
authors.initials: P
authors.lastname: Kettunen
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Banote
authors.forename: Emelie
authors.initials: E
authors.lastname: Lott
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Anders
authors.initials: A
authors.lastname: Arner
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal; D019521:Body Patterning; D054351:Electrical Synapses / Q000378:metabolism* / Q000473:pathology; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D008124:Locomotion / Q000502:physiology; D060172:Morpholinos / Q000008:administration & dosage; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis; D013550:Swimming; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D060172:Morpholinos; D029961:Zebrafish Proteins
keywords: Amyloid; Appb; Development; Locomotion; Motor neuron; Zebrafish