title: Amyloid precursor protein is required for convergent-extension movements during Zebrafish development.
abstract: Amyloid precursor protein (APP) has been a focus of intense investigation because of its role in Alzheimer's disease (AD), however, its biological function remains uncertain. Loss of APP and APP-like proteins results in postnatal lethality in mice, suggesting a role during embryogenesis. Here we show that in a zebrafish model system, knock down of APP results in the generation of fish with dramatically reduced body length and a short, curly tail. In situ examination of gene expression suggests that the APP morphant embryos have defective convergent-extension movements. We also show that wild-type human APP rescues the morphant phenotype, but the Swedish mutant APP, which causes familial AD (fAD), does not rescue the developmental defects. Collectively, this work demonstrates that the zebrafish model is a powerful system to define the role of APP during embryonic development and to evaluate the functional activity of fAD mutant APP.
authors: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic NC-30, Cleveland, OH 44195, USA.
authors: Powrnima
authors: P
authors: Joshi
authors: Jennifer O
authors: JO
authors: Liang
authors: Kristine
authors: K
authors: DiMonte
authors: John
authors: J
authors: Sullivan
authors: Sanjay W
authors: SW
authors: Pimplikar
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins