title: Amigo adhesion protein regulates development of neural circuits in zebrafish brain.
abstract: The Amigo protein family consists of three transmembrane proteins characterized by six leucine-rich repeat domains and one immunoglobulin-like domain in their extracellular moieties. Previous in vitro studies have suggested a role as homophilic adhesion molecules in brain neurons, but the in vivo functions remain unknown. Here we have cloned all three zebrafish amigos and show that amigo1 is the predominant family member expressed during nervous system development in zebrafish. Knockdown of amigo1 expression using morpholino oligonucleotides impairs the formation of fasciculated tracts in early fiber scaffolds of brain. A similar defect in fiber tract development is caused by mRNA-mediated expression of the Amigo1 ectodomain that inhibits adhesion mediated by the full-length protein. Analysis of differentiated neural circuits reveals defects in the catecholaminergic system. At the behavioral level, the disturbed formation of neural circuitry is reflected in enhanced locomotor activity and in the inability of the larvae to perform normal escape responses. We suggest that Amigo1 is essential for the development of neural circuits of zebrafish, where its mechanism involves homophilic interactions within the developing fiber tracts and regulation of the Kv2.1 potassium channel to form functional neural circuitry that controls locomotion.
authors.affiliation: From the Neuroscience Center.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: From the Neuroscience Center.
authors.forename: Juha
authors.initials: J
authors.lastname: Kuja-Panula
authors.affiliation: From the Neuroscience Center, Institute of Biomedicine/Anatomy, and.
authors.forename: Maria
authors.initials: M
authors.lastname: Sundvik
authors.affiliation: From the Neuroscience Center, Institute of Biomedicine/Anatomy, and.
authors.forename: Yu-Chia
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Institute of Biomedicine/Physiology, University of Helsinki, Helsinki FIN-00014, Finland.
authors.forename: Vilma
authors.initials: V
authors.lastname: Aho
authors.affiliation: From the Neuroscience Center.
authors.forename: Marjaana A
authors.initials: MA
authors.lastname: Peltola
authors.affiliation: Institute of Biomedicine/Physiology, University of Helsinki, Helsinki FIN-00014, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Porkka-Heiskanen
authors.affiliation: From the Neuroscience Center, Institute of Biomedicine/Anatomy, and.
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
authors.affiliation: From the Neuroscience Center, heikki.rauvala@helsinki.fi.
authors.forename: Heikki
authors.initials: H
authors.lastname: Rauvala
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D008297:Male; D009415:Nerve Net / Q000254:growth & development / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051669:Shab Potassium Channels / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C000592112:Amigo1 protein, zebrafish; D015816:Cell Adhesion Molecules, Neuronal; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D029961:Zebrafish Proteins
keywords: Amigo Protein Family; Axon; Axonal Scaffold; Brain; Kv2.1 Potassium Channel; Leucine-rich Repeat; Neurite Outgrowth; Neurobiology; Neurodevelopment; Zebrafish