Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues

Abstract

Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult.

Connecting muscle development, birth defects, and evolution: An essential role for muscle connective tissue

“…The tendons are the tensional links between the bones and muscles. The muscle connective tissue (MCT, sometimes called dense irregular connective tissue; Nassari et al, 2017) is the muscle’s closest anatomical and functional partner (Figure 2B). MCT is composed of three layers: the endomysium ensheathes individual myofibers, the perimysium bundles myofibers into fascicles, and the epimysium surrounds anatomical muscles and links to the tendons at the myotendinous junctions (Sanes, 2004).…”

“…Since embryonic Osr1+ cells have been explicitly shown to give rise to FAPs (Vallecillo-García et al, 2017) and most adult MCT fibroblasts express Tcf4 and PDGFRα and activated FAPs express Osr1 (Murphy et al, 2011; Stumm et al, 2018; Uezumi et al, 2010), MCT fibroblasts and FAPs are likely the same cell population. However, molecular heterogeneity and sub-populations within these fibroblasts undoubtedly exist (also see discussions in Nassari et al, 2017; Wosczyna and Rando, 2018). …”

Neural crest and the origin of species‐specific pattern

“…A broad range of prior investigations have revealed that cranial neural crest mesenchyme plays a critical role during muscle development. In particular, the early migration, differentiation, and spatial patterning of myogenic mesenchyme in the head relies on interactions with surrounding muscle connective tissues (Borue & Noden, 2004;Ericsson, Cerny, Falck, & Olsson, 2004;Francis-West et al, 2003;Grammatopoulos et al, 2000;Grenier, Teillet, Grifone, Kelly, & Duprez, 2009;Hall, 1950;Knight, Mebus, & Roehl, 2008;Knight & Schilling, 2006;Köntges & Lumsden, 1996;McGurk et al, 2017;Nassari, Duprez, & Fournier-Thibault, 2017;Noden, 1983Noden, , 1986aNoden, , 1988Noden, Marcucio, Borycki, & Emerson, 1999;Noden & Schneider, 2006;Noden & Trainor, 2005;Olsson, Falck, Lopez, Cobb, & Hanken, 2001;Pasqualetti et al, 2000;Rinon et al, 2007;Schilling et al, 1996;Schnorrer & Dickson, 2004;Subramanian & Schilling, 2015;Sugii et al, 2017;Tokita, Nakayama, Schneider, & Agata, 2013;Trainor & Krumlauf, 2000;Trainor, Sobieszczuk, Wilkinson, & Krumlauf, 2002;Tzahor et al, 2003).…”

Nuclear FGFR2 regulates musculoskeletal integration within the developing limb

“…Muscle connective tissue fibroblasts regulate muscle morphogenesis by establishing a prepattern for the muscle that the migrating myoblasts follow (Jacob et al, 1979;Chevallier and Kieny, 1982;Kardon, 1998;Kardon et al, 2003;Nassari et al, 2017). In conjunction, connective tissue fibroblasts contribute to the tendons, which mediate muscle-to-bone attachment at their origin and insertion and provide boundaries for muscle formation (Kardon, 1998).…”