Amyloid precursor protein is required for convergent-extension movements during Zebrafish development

Powrnima Joshi, Jennifer O. Liang, Kristine DiMonte, John Sullivan, Sanjay W. Pimplikar

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalDevelopmental Biology
Volume335
Issue number1
DOIs
StatePublished - Nov 1 2009

Bibliographical note

Funding Information:
We thank Dr. Carl-Philipp Heisenberg for providing us with RNA probes and helpful suggestions. Drs. Ron Conlon and Chris Nelson are thanked for their critical comments on this manuscript. This work was supported by a grant from an Anonymous Foundation and institutional support from Cleveland Clinic to SWP.

Keywords

  • APPswe
  • Amyloid precursor protein
  • Convergent extension
  • Embryonic development
  • Function
  • Gastrulation
  • Zebrafish

Fingerprint

Dive into the research topics of 'Amyloid precursor protein is required for convergent-extension movements during Zebrafish development'. Together they form a unique fingerprint.

Cite this