Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth
- Authors
- Song, P., and Pimplikar, S.W.
- ID
- ZDB-PUB-120503-12
- Date
- 2012
- Source
- PLoS One 7(4): e34209 (Journal)
- Registered Authors
- Song, Ping
- Keywords
- Embryos, Neurons, Zebrafish, Axons, Motor neurons, Phenotypes, Larvae, Cytoskeleton
- MeSH Terms
-
- Alzheimer Disease/genetics*
- Alzheimer Disease/pathology
- Amyloid beta-Protein Precursor/genetics*
- Amyloid beta-Protein Precursor/therapeutic use
- Animals
- Axons/metabolism
- Axons/pathology*
- Cells, Cultured
- Gene Expression Regulation, Developmental
- Gene Knockdown Techniques*
- Humans
- Motor Neurons/metabolism
- Motor Neurons/pathology*
- Mutation
- Phenotype
- Zebrafish/embryology
- Zebrafish/genetics*
- PubMed
- 22545081 Full text @ PLoS One
Amyloid precursor protein (APP) plays a pivotal role in Alzheimer’s disease (AD) pathogenesis, but its normal physiological functions are less clear. Combined deletion of the APP and APP-like protein 2 (APLP2) genes in mice results in post-natal lethality, suggesting that APP performs an essential, if redundant, function during embryogenesis. We previously showed that injection of antisense morpholino to reduce APP levels in zebrafish embryos caused convergent-extension defects. Here we report that a reduction in APP levels causes defective axonal outgrowth of facial branchiomotor and spinal motor neurons, which involves disorganized axonal cytoskeletal elements. The defective outgrowth is caused in a cell-autonomous manner and both extracellular and intracellular domains of human APP are required to rescue the defective phenotype. Interestingly, wild-type human APP rescues the defective phenotype but APPswe mutation, which causes familial AD, does not. Our results show that the zebrafish model provides a powerful system to delineate APP functions in vivo and to study the biological effects of APP mutations.