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Keep Your Friends Close: Cell–Cell Contact and Skeletal Myogenesis

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Keep Your Friends Close: Cell–Cell Contact and Skeletal Myogenesis Downloaded from http://cshperspectives.cshlp.org/ on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Keep Your Friends Close: Cell–Cell Contact and Skeletal Myogenesis Robert S. Krauss, Giselle A. Joseph, and Aviva J. Goel Department of Cell, Developmental, and Regenerative Biology, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029 Correspondence: [email protected] Development of skeletal muscle is a multistage process that includes lineage commitment of multipotent progenitor cells, differentiation and fusion of myoblasts into multinucleated myofibers, and maturation of myofibers into distinct types. Lineage-specific transcriptional regulation lies at the core of this process, but myogenesis is also regulated by extracellular cues. Some of these cues are initiated by direct cell–cell contact between muscle precursor cells themselves or between muscle precursors and cells of other lineages. Examples of the latter include interaction of migrating neural crest cells with multipotent muscle progenitor cells, muscle interstitial cells with myoblasts, and neurons with myofibers. Among the sig- naling factors involved are Notch ligands and receptors, cadherins, Ig superfamily members, and Ephrins and Eph receptors. In this article we describe recent progress in this area and highlight open questions raised by the findings. keletal muscle is the most abundant tissue in based on expression of distinct myosin heavy Sthe vertebrate body and necessary for breath- chain (MyHC) isoforms and metabolic capabil- ing, metabolic homeostasis, and locomotion. ities (Schiaffino and Reggiani 2011; Talbot and Development of skeletal muscle occurs in a se- Maves 2016). quential, multistage process that includes spec- Myogenic specification and differentiation ification of multipotent progenitors to lineage- are coordinated by the myogenic basic helix– committed myoblasts, differentiation of myo- loop–helix (bHLH) transcription factors Myf5, blasts into multinucleated myofibers, and mat- MyoD, myogenin, and MRF4. Uncommitted uration of myofibers by innervation and bun- progenitor cells are specified to become line- dling into functional muscles (Biressi et al. age-committed myoblasts through the com- 2007; Comai and Tajbakhsh 2014; Tintignac bined actions of Myf5, MRF4, and MyoD, et al. 2015). Myoblast differentiation is itself a whereas differentiation of myoblasts is regulated complex process that involves both induction of by myogenin, MyoD, and MRF4 (Tapscott2005; the muscle-specific transcriptome and fusion of Biressi et al. 2007; Comai and Tajbakhsh 2014). myoblasts into an elongated syncytium. Simi- Expression of these factors, particularly MyoD, larly, maturation is multifaceted. Mature myo- in many nonmuscle cell types converts such cells fibers are classified as “slow” or “fast” types, to the skeletal muscle program, revealing their Editors: Carien M. Niessen and Alpha S. Yap Additional Perspectives on Cell–Cell Junctions available at www.cshperspectives.org Copyright # 2017 Cold Spring Harbor Laboratory Press; all rights reserved Advanced Online Article. Cite this article as Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a029298 1 Downloaded from http://cshperspectives.cshlp.org/ on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press R.S. Krauss et al. ability to drive tissue-specific transcription and dermomyotome, which has epithelial character cell differentiation (Tapscott 2005; Fong and and gives rise to skeletal muscle and dermis, and Tapscott2013). The ability of MyoD to function ventrally into the sclerotome, which has mesen- in this manner occurs in conjunction with non- chymal character and gives rise to the bones and muscle-specific factors such as its heterodimeric cartilage of the axial skeleton (Brand-Saberi and partners, the E proteins; members of the Mef2 Christ 2000). Some dermomyotomal progenitor family of transcription factors; transcriptional cells undergo an epithelial-mesenchymal transi- coactivators; and chromatin remodeling factors tion (EMT), become committed to the skeletal (Tapscott 2005; Biressi et al. 2007; Sartorelli and muscle lineage, and migrate between the dermo- Juan 2011; Fong and Tapscott 2013; Comai and myotome and sclerotome to form the myotome, Tajbakhsh 2014). These and additional tran- a set of differentiated embryonic muscle cells. scription factors orchestrate development of Subsequent embryonic, fetal, and postnatal the skeletal muscle lineage. stages of myogenesis involve additional muscle Although the importance of lineage-specific progenitorsthat originally migrate from the der- transcriptional regulation in skeletal myogene- momyotome and ultimately establish the trunk sis has long been appreciated, myogenesis is also and limb musculature (Biressi et al. 2007; Comai regulated by extracellular cues that initiate in- and Tajbakhsh 2014). tracellular signaling (Guasconi and Puri 2009). Signals from the adjacent dorsal neural tube Some of these extracellular cues are secreted fac- and surface ectoderm play important roles in tors, such as fibroblast growth factor (Fgf ), Wnt maturation of the dorsal somite (Munsterberg family ligands, and Sonic hedgehog (Shh). A and Lassar 1995; Stern and Hauschka 1995). growing body of evidence indicates that signal- These tissues secrete Wnt1 and Wnt3a, which ing initiated by direct cell–cell contact also pro- signal via the “canonical” pathway to stimu- vides key regulatory information during devel- late b-catenin/T-cell factor (TCF)–dependent opment of the skeletal muscle lineage. In adult transcription. These Wnt ligands promote myo- skeletal muscle, stable cell–cell junctions (ex- genesis of explanted epithelial somites in vitro emplified by epithelial, cadherin-based adhe- (Munsterberg et al. 1995; Stern et al. 1995; Taj- rens junctions) do not appear to exist between bakhsh et al. 1998; Borello et al. 2006). Further- myofibers, which are the unit cells of this tissue. more, an enhancer that regulates Myf5 expres- (Cell–cell junctions do exist between myofibers sion in the dorsal somite harbors TCF binding and skeletal muscle stem cells known as satellite sites that are critical for Wnt responsiveness and cells; this is discussed below.) Nevertheless, enhancer function (Borello et al. 2006) (N.B.: cell–cell adhesion, and signaling that derives Myf5 is the first myogenic bHLH factor ex- from cell–cell contact, occurs between various pressed during development, and its role is muscle precursor cells and between these cells solely in lineage determination.) These results and nonmuscle cell types during myogenesis. argued that canonical Wnt ligands, along with Furthermore, such interactions are important Shh and soluble bone morphogenetic protein for muscle development. In this review, we dis- (BMP) inhibitors (Munsterberg et al. 1995; Re- cuss the roles and mechanisms whereby cell– shef et al. 1998; Borycki et al. 1999), induce cell contact regulates skeletal myogenesis. muscle lineage specification of dermomyotomal progenitor cells via b-catenin/TCF-dependent expression of Myf5. PROGENITOR CELL COMMITMENT TO THE b-catenin is well known for having two dis- SKELETAL MUSCLE CELL LINEAGE tinct cellular functions: (1) as a transcriptional In vertebrates, skeletal muscles of the trunk and regulator that associates with the DNA-binding limbs develop from somites, transiently existing TCF proteins in a Wnt signaling-responsive blocks of columnar epithelial cells that form in manner; and (2) as an adaptor protein that an anterior-to-posterior manner from paraxial binds to the cytoplasmic tail of cadherins and mesoderm. Somites mature dorsally into the promotes linkage to the cytoskeleton (van 2 Advanced Online Article. Cite this article as Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a029298 Downloaded from http://cshperspectives.cshlp.org/ on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Cell–Cell Contact and Skeletal Myogenesis Amerongen and Nusse 2009; Niessen et al. of the dermomyotome express Notch receptors 2011). Cells of the epithelial dermomyotome (Rios et al. 2011). Transient cell–cell contact express the cell–cell adhesion molecule N-cad- between migrating, Delta1þ neural crest cells herin with an apical localization; its adhesive and Notchþ muscle progenitors in the dermo- junction partner, b-catenin, is localized there myotome leads to Notch signaling in the latter. as well (Cinnamon et al. 2006). Studies with This is, in turn, required for Myf5 induction and chick embryos suggest that changes in N-cad- adoption of the skeletal muscle cell fate (Rios herin expression and subcellular localization et al. 2011). This “kiss and run” mode of cell– play important roles in specification of multi- cell contact-dependent signaling strongly sug- potent dermomyotomal cells to the muscle lin- gests that the concurrent timing of neural crest eage. As these cells divide, N-cadherin is asym- cell migration and myotome formation is mech- metrically localized in cells that are fated to anistically linked. become skeletal muscle cells of the myotome; Canonical Notch signaling involves cleavage conversely, daughter cells that lack N-cadherin of its intracellular domain (NICD), which take on features of early dermal cells (Cinna- translocates to the nucleus and binds RBP-J to mon et al. 2006). Consistent with these obser- stimulate pathway-responsive gene expression vations, electroporation of wild-type or domi- (Fortini 2009). In exploring how Notch signal-
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