Abstract

BackgroundSkeletal muscle differentiation requires assembly of contractile proteins into organized myofibrils. The Drosophila ladybird homeobox gene (lad) functions in founder cells of the segmental border muscle to promote myoblast fusion and muscle shaping. Tetrapods have two homologous genes (Lbx). Lbx1 functions in migration and/or proliferation of hypaxial myoblasts, whereas the function of Lbx2 is poorly understood.ResultsTo elucidate the role of Lbx in vertebrate myogenesis, we examined Lbx function in zebrafish. Zebrafish lbx2 transcripts appear in newly formed paraxial mesoderm and become restricted to adaxial cells, precursors of slow muscle. Slow muscles lose lbx2 expression as they differentiate, while a subset of differentiating fast muscle cells transiently expresses lbx2. Fin and hyoid muscle express lbx2 later. In contrast, lbx1b expression first appears lateral to the somites at late segmentation stages and is later restricted to fin muscle. Morpholino knockdown of Lbx1b and Lbx2 suppresses hypaxial muscle development. Moreover, knockdown of Lbx2 results in malformation of muscle fibers and reduced fusion of fast precursors, although no obvious effects on induction or specification are observed. Expression of myofilament genes, including actin and myosin, requires the engrailed repressor domain of Lbx2.ConclusionOur results elucidate a new function of Lbx2 as a regulator of myofibril formation.

Highlights

  • Skeletal muscle differentiation requires assembly of contractile proteins into organized myofibrils

  • Slow and fast muscle precursors transiently express lbx2 mRNA To study the function of lbx genes in vertebrate skeletal muscle development, we examined expression of lbx1b and lbx2 in zebrafish

  • By the end of bud stage, lbx2 expression appears in paraxial mesoderm and adaxial cells (Fig. 1C, J, brackets), precursors of slow muscle cells and muscle pioneers [18]. lbx2 expression is not detected in

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Summary

Introduction

Skeletal muscle differentiation requires assembly of contractile proteins into organized myofibrils. The Drosophila ladybird homeobox gene (lad) functions in founder cells of the segmental border muscle to promote myoblast fusion and muscle shaping. Skeletal muscle progenitors are specified as a population of multipotent mesodermal cells. These cells subsequently commit to a muscle fate and differentiate into muscle fibers by cell fusion and assembly of contractile myofibrils composed of myosin thick filaments and actin thin filaments. The molecular mechanisms that regulate induction of muscle progenitors, commitment of these cells to the muscle lineage, and myoblast fusion are well characterized [1,2,3,4,5], relatively less is known about the mechanisms that regulate the formation of myofibrils [6,7]. Recent studies showed that Lbx is required for establishment of morphological, ultrastructural, and functional properties of leg muscles in Drosophila [10]

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