asb11 is a regulator of embryonic and adult regenerative myogenesis
- Authors
- Tee, J.M., Sartori da Silva, M., Rygiel, A., Muncan, V., Bink, R., van den Brink, G., van Tijn, P., Zivkovic, D., Kodach, L., Guardavaccaro, D., Diks, S., and Peppelenbosch, M.
- ID
- ZDB-PUB-120423-3
- Date
- 2012
- Source
- Stem cells and development 21(17): 3091-3103 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Alleles
- Animals
- Blastomeres/cytology
- Blastomeres/metabolism
- Cell Count
- Cell Differentiation
- Cell Proliferation
- Cells, Cultured
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental*
- Germ-Line Mutation
- Immunohistochemistry
- Mice
- Models, Animal
- Muscle Development*
- Muscle, Skeletal/cytology
- Muscle, Skeletal/injuries
- Muscle, Skeletal/metabolism
- PAX7 Transcription Factor/genetics
- PAX7 Transcription Factor/metabolism
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Regeneration*
- Satellite Cells, Skeletal Muscle/cytology
- Satellite Cells, Skeletal Muscle/metabolism
- Suppressor of Cytokine Signaling Proteins/genetics
- Suppressor of Cytokine Signaling Proteins/metabolism*
- Transfection
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 22512762 Full text @ Stem Cells Dev.
The specific molecular determinants that govern progenitor expansion and final compartment size in the myogenic lineage, either during gestation or during regenerative myogenesis, remain largely obscure. Recently, we retrieved d-asb11 from a zebrafish screen designed to identify gene products that are down regulated during embryogenesis upon terminal differentiation and identified it as a potential regulator of compartment size in the ectodermal lineage. A role in mesodermal derivatives remained, however, unexplored. Here we report pan-vertebrate expression of Asb11 in muscle compartments, where it highly specifically localises to the Pax7+ muscle satellite cell compartment. Forced expression of d-asb11 impaired terminal differentiation and caused enhanced proliferation in the myogenic progenitor compartment both in in vivo and in vitro model systems. Conversely, introduction of a germline hypomorphic mutation in the zebrafish d-asb11 gene produced premature differentiation of the muscle progenitors and delayed regenerative responses in adult injured muscle. The expression of d-asb11 being necessary for muscle progenitor expansion, whereas its down regulation marks the onset of terminal differentiation. Hence, we provide evidence that d-asb11 is a principal regulator of embryonic as well as adult regenerative myogenesis.