title: asb11 is a regulator of embryonic and adult regenerative myogenesis.
abstract: 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 downregulated 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 localizes 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. Thus, the expression of d-asb11 is necessary for muscle progenitor expansion, whereas its downregulation 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.
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Tee
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sartori da Silva
authors.forename: Agnieszka M
authors.initials: AM
authors.lastname: Rygiel
authors.forename: Vanesa
authors.initials: V
authors.lastname: Muncan
authors.forename: Robert
authors.initials: R
authors.lastname: Bink
authors.forename: Gijs R
authors.initials: GR
authors.lastname: van den Brink
authors.forename: Paula
authors.initials: P
authors.lastname: van Tijn
authors.forename: Danica
authors.initials: D
authors.lastname: Zivkovic
authors.forename: Liudmila L
authors.initials: LL
authors.lastname: Kodach
authors.forename: Daniele
authors.initials: D
authors.lastname: Guardavaccaro
authors.forename: Sander H
authors.initials: SH
authors.lastname: Diks
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
mesh_terms: D000483:Alleles; D000818:Animals; D001757:Blastomeres / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018095:Germ-Line Mutation; D007150:Immunohistochemistry; D051379:Mice; D023421:Models, Animal; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C514282:Asb11 protein, zebrafish; D051763:PAX7 Transcription Factor; D012333:RNA, Messenger; D050826:Suppressor of Cytokine Signaling Proteins; D029961:Zebrafish Proteins