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PLoS One. 2014 Jun 12;9(6):e99210. doi: 10.1371/journal.pone.0099210. eCollection 2014.

Zebrafish ambra1a and ambra1b knockdown impairs skeletal muscle development.

Author information

1
Department of Biology, University of Padova, Padova, Italy.
2
Department of Molecular Medicine, University of Padova, Padova, Italy.
3
Department of Biology, University of Tor Vergata, Rome, Italy.
4
Department of Biology, University of Tor Vergata, Rome, Italy; Department of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico "Santa Lucia Foundation", Rome, Italy; Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark.

Erratum in

  • PLoS One. 2014;9(9):e109480.

Abstract

The essential role of autophagy in muscle homeostasis has been clearly demonstrated by phenotype analysis of mice with muscle-specific inactivation of genes encoding autophagy-related proteins. Ambra1 is a key component of the Beclin 1 complex and, in zebrafish, it is encoded by two paralogous genes, ambra1a and ambra1b, both required for normal embryogenesis and larval development. In this study we focused on the function of Ambra1, a positive regulator of the autophagic process, during skeletal muscle development by means of morpholino (MO)-mediated knockdown and compared the phenotype of zebrafish Ambra1-depleted embryos with that of Ambra1gt/gt mouse embryos. Morphological analysis of zebrafish morphant embryos revealed that silencing of ambra1 impairs locomotor activity and muscle development, as well as myoD1 expression. Skeletal muscles in ATG-morphant embryos displayed severe histopathological changes and contained only small areas of organized myofibrils that were widely dispersed throughout the cell. Double knockdown of ambra1a and ambra1b resulted in a more severe phenotype whereas defects were much less evident in splice-morphants. The morphants phenotypes were effectively rescued by co-injection with human AMBRA1 mRNA. Together, these results indicate that ambra1a and ambra1b are required for the correct development and morphogenesis of skeletal muscle.

PMID:
24922546
PMCID:
PMC4055674
DOI:
10.1371/journal.pone.0099210
[Indexed for MEDLINE]
Free PMC Article

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