Integrin α6β1-laminin interactions regulate early myotome formation in the mouse embryo

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Abstract
We addressed the potential role of cell-laminin interactions during epaxial myotome formation in the mouse embryo. Assembly of the myotomal laminin matrix occurs as epaxial myogenic precursor cells enter the myotome. Most Myf5-positive and myogenin-negative myogenic precursor cells localise near assembled laminin, while myogenin-expressing cells are located either away from this matrix or in areas where it is being assembled. In Myf5nlacZ/nlacZ (Myf5-null) embryos, laminin, collagen type IV and perlecan are present extracellularly near myogenic precursor cells, but do not form a basement membrane and cells are not contained in the myotomal compartment. Unlike wild-type myogenic precursor cells, Myf5-null cells do not express the α6β1 integrin, a laminin receptor, suggesting that integrin α6β1-laminin interactions are required for myotomal laminin matrix assembly. Blockingα 6β1-laminin binding in cultured wild-type mouse embryo explants resulted in dispersion of Myf5-positive cells, a phenotype also seen in Myf5nlacZ/nlacZ embryos. Furthermore, inhibition ofα 6β1 resulted in an increase in Myf5 protein and ectopic myogenin expression in dermomyotomal cells, suggesting that α6β1-laminin interactions normally repress myogenesis in the dermomyotome. We conclude that Myf5 is required for maintaining α6β1 expression on myogenic precursor cells, and that α6β1 is necessary for myotomal laminin matrix assembly and cell guidance into the myotome. Engagement of laminin byα 6β1 also plays a role in maintaining the undifferentiated state of cells in the dermomyotome prior to their entry into the myotome.