title: Inhibition of myoblast migration via decorin expression is critical for normal skeletal muscle differentiation.
abstract: During limb skeletal muscle formation, committed muscle cells proliferate and differentiate in the presence of extracellular signals that stimulate or repress each process. Proteoglycans are extracellular matrix organizers and modulators of growth factor activities, regulating muscle differentiation in vitro. Previously, we characterized proteoglycan expression during early limb muscle formation and showed a spatiotemporal relation between the onset of myogenesis and the expression of decorin, an important muscle extracellular matrix component and potent regulator of TGF-beta activity. To evaluate decorin's role during in vivo differentiation in committed muscle cells, we grafted wild type and decorin-null myoblasts onto chick limb buds. The absence of decorin enhanced the migration and distribution of myoblasts in the limb, correlating with the inhibition of skeletal muscle differentiation. Both phenotypes were reverted by de novo decorin expression. In vitro, we determined that both decorin core protein and its glycosaminoglycan chain were required to reverse the migration phenotype. Results presented here suggest that the enhanced migration observed in decorin-null myoblasts may not be dependent on chemotactic growth factor signaling nor the differentiation status of the cells. Decorin may be involved in the establishment and/or coordination of a critical myoblast density, through inhibition of migration, that permits normal muscle differentiation during embryonic myogenesis.
authors.affiliation: Centro de Regulación Celular y Patología, Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biológicas, MIFAB, P. Universidad Católica de Chile, Santiago, Chile.
authors.forename: Hugo C
authors.initials: HC
authors.lastname: Olguin
authors.forename: Cristian
authors.initials: C
authors.lastname: Santander
authors.forename: Enrique
authors.initials: E
authors.lastname: Brandan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D017690:Cell Transplantation; D002642:Chick Embryo; D018920:Coculture Techniques; D058575:Decorin; D016326:Extracellular Matrix Proteins; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D018878:Limb Buds / Q000166:cytology / Q000254:growth & development; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D018008:Myogenin / Q000378:metabolism; D011509:Proteoglycans / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014183:Transplantation, Heterologous; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; C503801:Myog protein, mouse; D018008:Myogenin; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D001616:beta-Galactosidase