Zebrafish ambra1a and ambra1b knockdown impairs skeletal muscle development

Tatjana Skobo, Francesca Benato, Paolo Grumati, Giacomo Meneghetti, Valentina Cianfanelli, Silvia Castagnaro, Martina Chrisam, Sabrina Di Bartolomeo, Paolo Bonaldo, Francesco Cecconi, Luisa Dalla Valle

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Article numbere99210
JournalPLoS One
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 12 2014

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Muscle Development
muscle development
Zebrafish
Danio rerio
Muscle
skeletal muscle
embryo (animal)
Skeletal Muscle
Embryonic Structures
Phenotype
phenotype
autophagy
Morpholinos
Muscles
muscles
Myofibrils
myofibrils
mice
Autophagy
Gene Silencing

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Skobo, T., Benato, F., Grumati, P., Meneghetti, G., Cianfanelli, V., Castagnaro, S., ... Dalla Valle, L. (2014). Zebrafish ambra1a and ambra1b knockdown impairs skeletal muscle development. PLoS One, 9(6), [e99210]. https://doi.org/10.1371/journal.pone.0099210

Zebrafish ambra1a and ambra1b knockdown impairs skeletal muscle development. / Skobo, Tatjana; Benato, Francesca; Grumati, Paolo; Meneghetti, Giacomo; Cianfanelli, Valentina; Castagnaro, Silvia; Chrisam, Martina; Di Bartolomeo, Sabrina; Bonaldo, Paolo; Cecconi, Francesco; Dalla Valle, Luisa.

In: PLoS One, Vol. 9, No. 6, e99210, 12.06.2014.

Research output: Contribution to journalArticle

Skobo, T, Benato, F, Grumati, P, Meneghetti, G, Cianfanelli, V, Castagnaro, S, Chrisam, M, Di Bartolomeo, S, Bonaldo, P, Cecconi, F & Dalla Valle, L 2014, 'Zebrafish ambra1a and ambra1b knockdown impairs skeletal muscle development', PLoS One, vol. 9, no. 6, e99210. https://doi.org/10.1371/journal.pone.0099210
Skobo T, Benato F, Grumati P, Meneghetti G, Cianfanelli V, Castagnaro S et al. Zebrafish ambra1a and ambra1b knockdown impairs skeletal muscle development. PLoS One. 2014 Jun 12;9(6). e99210. https://doi.org/10.1371/journal.pone.0099210
Skobo, Tatjana ; Benato, Francesca ; Grumati, Paolo ; Meneghetti, Giacomo ; Cianfanelli, Valentina ; Castagnaro, Silvia ; Chrisam, Martina ; Di Bartolomeo, Sabrina ; Bonaldo, Paolo ; Cecconi, Francesco ; Dalla Valle, Luisa. / Zebrafish ambra1a and ambra1b knockdown impairs skeletal muscle development. In: PLoS One. 2014 ; Vol. 9, No. 6.
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