Retrograde migration of pectoral girdle muscle precursors depends on CXCR4/SDF-1 signaling

Abstract

In vertebrates, muscles of the pectoral girdle connect the forelimbs with the thorax. During development, the myogenic precursor cells migrate from the somites into the limb buds. Whereas most of the myogenic precursors remain in the limb bud to form the forelimb muscles, several cells migrate back toward the trunk to give rise to the superficial pectoral girdle muscles, such as the large pectoral muscle, the latissimus dorsi and the deltoid. Recently, this developing mode has been referred to as the "In-Out" mechanism. The present study focuses on the mechanisms of the "In-Out" migration during formation of the pectoral girdle muscles. Combining in ovo electroporation, tissue slice-cultures and confocal laser scanning microscopy, we visualize live in detail the retrograde migration of myogenic precursors from the forelimb bud into the trunk region by live imaging. Furthermore, we present for the first time evidence for the involvement of the chemokine receptor CXCR4 and its ligand SDF-1 during these processes. After microsurgical implantations of CXCR4 inhibitor beads in the proximal forelimb region of chicken embryos, we demonstrate with the aid of in situ hybridization and live-cell imaging that CXCR4/SDF-1 signaling is crucial for the retrograde migration of pectoral girdle muscle precursors. Moreover, we analyzed the MyoD expression in CXCR4-mutant mouse embryos and observed a considerable decrease in pectoral girdle musculature. We thus demonstrate the importance of the CXCR4/SDF-1 axis for the pectoral girdle muscle formation in avians and mammals.

Real-Time Imaging of Accessible Axon Guidance Assays in Three-Dimensional Culture

“…The test cells can be in the form of an organotypic culture such as an entire DRG/spinal cord explant, or they can be in the form of dissociated cells mixed into the gel before it polymerizes. The bead-based approach has the advantage of being directly comparable to in vivo experiments where the same beads are inserted into a developing chicken embryo to see its effect after continued development [20].…”

“…A disadvantage is that the steepness of the gradient diminishes over time, remaining effective within three days ( Figure 3E). Additionally, bead experiments can be directly replicated in vivo via chicken embryo bead implantation experiments using the exact same beads [20]. This would have the advantage of already having a perfectly working negative control model (a developing embryo), such that any effects on the nervous system can be observed in the context of its natural surroundings.…”

Development of the shoulder girdle musculature

“…In contrast, the shoulder girdle muscles have multiple myogenic sources, such as the ventrolateral lips of the dermomyotomes, the lateral plate mesoderm and, putatively, the myotomes. Beside the SF/c‐met and SDF‐1/CXCR4 signalling mechanisms controlling myogenic cell migration (Bladt et al, ; Brand‐Saberi et al, ; Vasyutina et al, ; Masyuk et al, ), mechanisms controlling head muscle development are also involved in the regulation of the shoulder girdle muscle formation (Pu et al, ). In this review, an overview of the development of the shoulder girdle muscle is presented.…”

SDF-1 controls the muscle and blood vessel formation of the somite

“…During the cloaca muscle formation, SDF-1 is required for the migration of myogenic precursor cells from the hind limb into the cloaca (Rehimi et al, 2008). SDF-1 plays the same role for the migration of myogenic precursor cells from the forelimb to the trunk during the formation of the shoulder girdle muscles (Masyuk et al, 2014). In addition, SDF-1 participates in muscle regeneration by inducing muscle progenitor/ satellite cell differentiation via both CXCR4 and CXCR7 signaling (Melechionna et al, 2010).…”