In vivo analyzes of dystroglycan function during somitogenesis in <i>Xenopus laevis</i>

Hidalgo, Magdalena; Sirour, Cathy; Bello, Valérie; Moreau, Nicole; Beaudry, Michèle; Darribère, Thierry

doi:10.1002/dvdy.21814

Cited by 20 publications

(19 citation statements)

References 47 publications

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“…Interestingly, disruption of ␤-dystroglycan or integrin-linked kinase in these species led to similar gross morphological defects and as those observed in our GRAF1 morphants (39 -41). However, the cause for fiber degeneration is distinct as depletion of integrin-linked kinase resulted in detachment of the intact cell from the matrix (39), whereas depletion of ␤-dystroglycan led to detachment within the sarcolemmal membrane plane (40,41), and depletion of GRAF1 led to severing of the contractile units.…”

Section: Discussionmentioning

confidence: 99%

Skeletal Muscle Differentiation and Fusion Are Regulated by the BAR-containing Rho-GTPase-activating Protein (Rho-GAP), GRAF1

Doherty

Lenhart

Cameron

et al. 2011

Journal of Biological Chemistry

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Although RhoA activity is necessary for promoting myogenic mesenchymal stem cell fates, recent studies in cultured cells suggest that down-regulation of RhoA activity in specified myoblasts is required for subsequent differentiation and myotube formation. However, whether this phenomenon occurs in vivo and which Rho modifiers control these later events remain unclear. We found that expression of the Rho-GTPase-activating protein, GRAF1, was transiently up-regulated during myogenesis, and studies in C2C12 cells revealed that GRAF1 is necessary and sufficient for mediating RhoA down-regulation and inducing muscle differentiation. Moreover, forced expression of GRAF1 in pre-differentiated myoblasts drives robust muscle fusion by a process that requires GTPase-activating protein-dependent actin remodeling and BAR-dependent membrane binding or sculpting. Moreover, morpholino-based knockdown studies in Xenopus laevis determined that GRAF1 expression is critical for muscle development. GRAF1-depleted embryos exhibited elevated RhoA activity and defective myofibrillogenesis that resulted in progressive muscle degeneration, defective motility, and embryonic lethality. Our results are the first to identify a GTPase-activating protein that regulates muscle maturation and to highlight the functional importance of BAR domains in myotube formation.Skeletal muscle development is a tightly regulated process involving the specification of mesodermal precursors into myoblasts and subsequent differentiation and fusion of these cells into multinucleated myotubes. Primary myogenesis is initiated in somites via the spatial and temporal expression of myogenic regulatory factors that include MyoD and Myf5, which are required for initial specification of skeletal myoblasts, and myogenin, MRF4, and myocyte-specific enhancer factors (MEF2a and MEF2c), which induce differentiation of these specified cells. Additional transcriptional control of skeletal muscle differentiation is imparted by serum-response factor, a MADS box-containing transcription factor that promotes both myoblast proliferation and expression of skeletal muscle marker genes (for review see Ref. 1).It is not completely clear how these myogenic regulatory factors are activated during development, but it is known that the small GTPase Rho (which can induce serum-response factordependent gene transcription) plays a role. RhoA was reported to both promote and interfere with the skeletal muscle differentiation program (for review see Ref.2). However, more recent studies in cultured cells suggest that RhoA activity must be tightly regulated in a finely coordinated time-dependent manner to ensure appropriate skeletal muscle formation (3-5). Specifically, these later studies showed that although RhoA activity is necessary for specification of myoblasts, down-regulation of RhoA activity in specified myoblasts is essential for subsequent cell cycle withdrawal, expression of skeletal muscle differentiation genes, and myotube fusion (i.e. secondary myogenesis). The mechanism by which ...

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Section: Discussionmentioning

confidence: 99%

Skeletal Muscle Differentiation and Fusion Are Regulated by the BAR-containing Rho-GTPase-activating Protein (Rho-GAP), GRAF1

Doherty

Lenhart

Cameron

et al. 2011

Journal of Biological Chemistry

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“…This process begins with cells at the anterior end of the PSM becoming progressively more elongated in the mediolateral axis (Afonin et al, 2006). This step is followed by the formation of the intersomitic boundary, which involves the deposition of critical extracellular matrix molecules such as laminin and fibronectin (Hidalgo et al, 2009). Soon after segmentation, individual cells within the somite undergo a 90° reorientation to form myotome fibers in parallel alignment with the notochord (Hamilton, 1969; Youn and Malancinski, 1981).…”

Section: Introductionmentioning

confidence: 99%

The Role of Sdf‐1α signaling in Xenopus laevis somite morphogenesis

Leal

Fickel

Sabillo

et al. 2013

Developmental Dynamics

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Background Stromal derived factor-1α (sdf-1α), a chemoattractant chemokine, plays a major role in tumor growth, angiogenesis, metastasis and in embryogenesis. The sdf-1α signaling pathway has also been shown to be important for somite rotation in zebrafish (Hollway, et al 2007). Given the known similarities and differences between zebrafish and Xenopus laevis somitogenesis, we sought to determine whether the role of sdf-1α is conserved in Xenopus laevis. Results Using a morpholino approach, we demonstrate that knockdown of sdf-1α or its receptor, cxcr4, leads to a significant disruption in somite rotation and myotome alignment. We further show that depletion of sdf-1α or cxcr4 leads to the near absence of β-dystroglycan and laminin expression at the intersomitic boundaries. Finally, knockdown of sdf-1α decreases the level of activated RhoA, a small GTPase known to regulate cell shape and movement. Conclusion Our results show that sdf-1α signaling regulates somite cell migration, rotation and myotome alignment by directly or indirectly regulating dystroglycan expression and RhoA activation. These findings support the conservation of sdf-1α signaling in vertebrate somite morphogenesis; however, the precise mechanism by which this signaling pathway influences somite morphogenesis is different between the fish and the frog.

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“…The proper scaffolding of fibronectin within the intersomitic boundary appears to be driven by integrin α5 expression during somite rotation [20]. This is followed by the deposition of laminin, whose assembly requires β-dystroglycan expression [21] (Fig. 1).…”

Section: Cell Movements Underlying Somite Formationmentioning

confidence: 99%

“…The last step involves the stable attachment of myotome fibers to the intersomitic boundary, thereby establishing an elongated and aligned morphology (Step 4). Adapted from [17] and [21]. …”

Section: Figurementioning

confidence: 99%

Making muscle: Morphogenetic movements and molecular mechanisms of myogenesis in Xenopus laevis

Sabillo

Ramirez

Domingo

2016

Seminars in Cell & Developmental Biology

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Xenopus laevis offers unprecedented access to the intricacies of muscle development. The large, robust embryos make it ideal for manipulations at both the tissue and molecular level. In particular, this model system facilitates the ability to fate map early muscle progenitors, visualize cell behaviors associated with somitogenesis, and examine the role of signaling pathways that underlie induction, specification, and differentiation of cells that comprise the musculature system. Several characteristics that are unique to X. laevis include myogenic waves with distinct gene expression profiles and the late formation of dermomyotome and sclerotome. Furthermore, myogenesis in the metamorphosing frog is biphasic, facilitating regeneration studies. In this review, we describe the morphogenetic movements that shape the somites and discuss signaling and transcriptional regulation during muscle development and regeneration. With recent advances in gene editing tools, X. laevis remains a premier model organism for dissecting the complex mechanisms underlying the specification, cell behaviors, and formation of the musculature system.

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In vivo analyzes of dystroglycan function during somitogenesis in Xenopus laevis

Cited by 20 publications

References 47 publications

Skeletal Muscle Differentiation and Fusion Are Regulated by the BAR-containing Rho-GTPase-activating Protein (Rho-GAP), GRAF1

Skeletal Muscle Differentiation and Fusion Are Regulated by the BAR-containing Rho-GTPase-activating Protein (Rho-GAP), GRAF1

The Role of Sdf‐1α signaling in Xenopus laevis somite morphogenesis

Making muscle: Morphogenetic movements and molecular mechanisms of myogenesis in Xenopus laevis

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