Integrin α6β1-laminin interactions regulate early myotome formation in the mouse embryo
Integrin α6β1-laminin interactions regulate early myotome formation in the mouse embryo
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DOI：
10.1242/dev.02336
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发表时间：
2006-05-01
期刊：
影响因子：
4.6
通讯作者：
Thorsteinsdóttir, S
中科院分区：
文献类型：
--
作者：
Bajanca, F;Luz, M;Thorsteinsdóttir, S
我们探讨了在小鼠胚胎轴上肌节形成过程中细胞-层粘连蛋白相互作用的潜在作用。肌节层粘连蛋白基质的组装发生在轴上肌源性前体细胞进入肌节时。大多数Myf 5阳性和肌细胞生成素阴性的肌原性前体细胞位于组装的层粘连蛋白附近，而肌细胞生成素表达细胞位于远离该基质或其组装的区域。在Myf 5（nlacZlnlacZ）（Myf 5-null）胚胎中，层粘连蛋白、IV型胶原蛋白和串珠蛋白聚糖存在于肌原性前体细胞附近的细胞外，但不形成基底膜，并且细胞不包含在肌节区室中。与野生型肌源性前体细胞不同，Myf 5-null细胞不表达α 6 β 1整联蛋白（一种层粘连蛋白受体），表明整联蛋白α 6 β 1-层粘连蛋白相互作用是肌瘤层粘连蛋白基质组装所需的。在培养的野生型小鼠胚胎外植体中阻断α 6 β 1-层粘连蛋白结合导致Myf 5阳性细胞的分散，这也是在Myf 5（nlacZlnlacZ）胚胎中观察到的表型。此外，α 6 β 1的抑制导致Myf 5蛋白和皮肌节细胞中异位肌生成素表达的增加，表明α 6 β 1-层粘连蛋白相互作用通常抑制皮肌节中的肌生成。我们的结论是Myf 5是维持α 6 β 1在肌源性前体细胞上表达所必需的，α 6 β 1是肌节层粘连蛋白基质组装和细胞引导进入肌节所必需的。层粘连蛋白与α 6 β 1的结合也在细胞进入肌节之前维持真皮肌节中细胞的未分化状态中起作用。
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 Myf5(nlacZlnlacZ) (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 alpha 6 beta 1 integrin, a laminin receptor, suggesting that integrin alpha 6 beta 1-laminin interactions are required for myotomal laminin matrix assembly. Blocking alpha 6 beta 1-laminin binding in cultured wild-type mouse embryo explants resulted in dispersion of Myf5-positive cells, a phenotype also seen in Myf5(nlacZlnlacZ) embryos. Furthermore, inhibition of alpha 6 beta 1 resulted in an increase in Myf5 protein and ectopic myogenin expression in dermomyotomal cells, suggesting that alpha 6 beta 1-laminin interactions normally repress myogenesis in the dermomyotome. We conclude that Myf5 is required for maintaining alpha 6 beta 1 expression on myogenic precursor cells, and that alpha 6 beta 1 is necessary for myotomal laminin matrix assembly and cell guidance into the myotome. Engagement of laminin by alpha 6 beta 1 also plays a role in maintaining the undifferentiated state of cells in the dermomyotome prior to their entry into the myotome.