Migration of myoblasts across basal lamina during skeletal muscle development

Abstract

Basal lamina is a sheet of extracellular matrix that separates cells into topologically distinct groups during morphogenesis and is thought to form a barrier to cell migration. We have examined whether, during normal muscle development, myoblasts--mononucleate muscle precursor cells--can cross the basal lamina that surrounds each multinucleate muscle fibre. We marked myoblasts in vivo by injecting replication-defective retroviral vectors encoding LacZ into muscle tissue and analysed the fate of their progeny by the expression of beta-galactosidase. A dual labelling method with broad application to retroviral lineage-marking studies was developed to ensure that most clusters of labelled cells were clones derived from a single precursor cell. Most of the myoblasts that were infected at a late stage of rat hindlimb development, when each fibre with its satellite myoblasts is individually encased in a basal lamina sheath, gave rise to clones that contributed to several labelled fibres. Our results show that myoblasts from healthy fibres migrate across basal lamina during normal development and could contribute to the repair of fibres damaged by injury or disease.