Making muscle: skeletal myogenesisin vivoandin vitro

Abstract

Skeletal muscle is the largest tissue in the body and loss of its function or its regenerative properties results in debilitating musculoskeletal disorders. Understanding the mechanisms that drive skeletal muscle formation will not only help to unravel the molecular basis of skeletal muscle diseases, but also provide a roadmap for recapitulating skeletal myogenesis in vitro from pluripotent stem cells (PSCs). PSCs have become an important tool for probing developmental questions, while differentiated cell types allow the development of novel therapeutic strategies. In this Review, we provide a comprehensive overview of skeletal myogenesis from the earliest premyogenic progenitor stage to terminally differentiated myofibers, and discuss how this knowledge has been applied to differentiate PSCs into muscle fibers and their progenitors in vitro.

A critical role for the nuclear protein Akirin2 in the formation of mammalian muscle in vivo

“…Shortly after the limb bud is established at ∼E10, Pax3‐positive cells migrate from the hypaxial division of the lateral dermomyotome into the nascent limb bud to form the pool of cells that generate limb skeletal muscle (Biressi, Molinaro, & Cossu, ). Upon migration of Pax3‐positive progenitor cells into the limb bud, the coordination of multiple transcription factors is required for correct myogenesis in mammals, including the muscle determination and differentiation factors Myf5, MyoD, MRF4, and myogenin (Chal & Pourquie, ).…”

“…The precursors for muscle development in vertebrates arise within the somites, which form sequentially in a rostral to caudal progression as segmented units derived from the paraxial mesoderm flanking the neural tube (Endo, 2015). Somites subsequently divide into a ventromedial sclerotome, which forms vertebrae, ribs and tendons, and a dorsolateral dermomyotome, which generates all skeletal muscle in the trunk and limb, as well as the dermis of the back and brown fat (Chal & Pourquie, 2017;Endo, 2015;Hubaud & Pourquie, 2014). Muscle progenitor cells are further divided into hypaxial cells, which form the muscles of the limb and body wall; and epaxial, which forms deep back muscle (Cheng, Alvares, Ahmed, El-Hanfy, & Dietrich, 2004).…”

Neural crest and the patterning of vertebrate craniofacial muscles

“…(2) Except for trunk axial muscles, myoblasts leave their sites of initial differentiation and move, usually as aggregated cohorts, into peripheral regions (reviewed by: Noden & Francis‐West, ; Tzahor & Evans, ). This process and (3) the subsequent myotube alignment, segregation of individual muscles, and attachment of myotubes to definitive connective tissues require “instructive” interactions from adjacent connective tissues (limbs: Kardon, ; Kardon, Harfe, & Tabin, ; Robson, Kara, Crawley, & Tickle, ; diaphragm: Merrell et al, ; jaw: McGurk et al, ; reviewed by: Chal & Pourquié, ; Deries & Thorsteinsdóttir, ). In some cases, those interactions are associated with differentiating cartilages or tendons, but often the cues are operating at earlier stages and are more cryptic, identified only through analyses of local transcription factors, for example, Tbx4 and Tbx5 genes in limb mesenchyme (Hasson et al, ).…”

In Vitro Tissue‐Engineered Skeletal Muscle Models for Studying Muscle Physiology and Disease

“…[16] Paraxial mesoderm specification and formation is regulated by FGF, Wnt and BMP signaling and results in the sequential expression of the early mesoderm marker T (Brachyury) and paraxial mesoderm markers mesogeninl, Tbx6 and Pax3 ( Figure 1 ). [16–18] The segmentation clock, which generates oscillations of FGF, Notch and Wnt signals, regulates somite formation from paraxial mesoderm progenitors. [19] The somite then develops into two distinct compartments, the ventral sclerotome that gives rise to cartilage and bone, and the dermomyotome that gives rise to skeletal muscle, brown fat, and dermis of the back.…”

“…[20] The dermomyotome consists of three distinct divisions, the central dermomyotome (which gives rise to brown fat, back dermis, and trunk muscles), the dorsomedial lip, and the ventrolateral lip. [16,19] The first muscle mass to form is the myotome, which forms from the delamination and migration of MPCs from the dorsomedial and ventrolateral lips. [21] Transcription factor Pax3, which is initially expressed in paraxial mesoderm progenitors, becomes restricted to the dermomyotome and induces expression of c-met, the functional receptor for HGF/SCF.…”