Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth.
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 essent...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0034209&type=printable |
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| author | Ping Song Sanjay W Pimplikar |
| author_facet | Ping Song Sanjay W Pimplikar |
| author_sort | Ping Song |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dc32f3aa93074959a8cce912867dffa1 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-dc32f3aa93074959a8cce912867dffa12025-08-20T02:43:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3420910.1371/journal.pone.0034209Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth.Ping SongSanjay W PimplikarAmyloid 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0034209&type=printable |
| spellingShingle | Ping Song Sanjay W Pimplikar Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth. PLoS ONE |
| title | Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth. |
| title_full | Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth. |
| title_fullStr | Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth. |
| title_full_unstemmed | Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth. |
| title_short | Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth. |
| title_sort | knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0034209&type=printable |
| work_keys_str_mv | AT pingsong knockdownofamyloidprecursorproteininzebrafishcausesdefectsinmotoraxonoutgrowth AT sanjaywpimplikar knockdownofamyloidprecursorproteininzebrafishcausesdefectsinmotoraxonoutgrowth |