Hirsch E, Lohikangas L, Gullberg D, Johansson S, Fässler R
Max Planck Institute for Biochemistry, Germany.
J Cell Sci. 1998 Aug;111 ( Pt 16):2397-409. doi: 10.1242/jcs.111.16.2397.
Antibody perturbation experiments suggested that migration, terminal differentiation and fusion of myoblasts are dependent on beta1 integrin expression. In addition, several studies have postulated that beta1 integrins have a role in the formation of sarcomeres. In the present report we have analysed skeletal myogenesis in wild-type/beta1-null chimeric mice and beta1-null embryoid bodies. Trunk and limbs of beta1-null chimeric mice contained muscle tissue composed of normal and beta1-null myoblasts indicating that all myotomic sublineages can form, migrate to their peripheral targets and fuse in the absence of beta1 integrin expression. Pure populations of beta1-null myoblasts and satellite cells isolated from beta1-null chimeric embryos and chimeric newborn mice, respectively, were able to differentiate in vitro and to fuse into multinucleated myotubes. Quantitative and qualitative comparisons between normal and beta1-null myoblasts revealed no apparent difference in their capacity to terminally differentiate and fuse. Furthermore, beta1-null myotubes developed sarcomeres which were indistinguishable from wild-type controls. When normal and beta1-null ES cells were differentiated into embryoid bodies, they contained fully differentiated myotubes with normal sarcomeres and normal deposition of costameric components. However, formation of beta1-null myotubes was delayed and was less efficient in beta1-null embryoid bodies than in wild-type controls. High expression of alphav integrin subunit at the tips of normal as well as beta1-null myotubes indicated that the lack of beta1 integrins did not result in a significant redistribution of alphav-containing receptors.
抗体干扰实验表明，成肌细胞的迁移、终末分化和融合依赖于β1整合素的表达。此外，多项研究推测β1整合素在肌节形成中起作用。在本报告中，我们分析了野生型/β1基因敲除嵌合小鼠和β1基因敲除类胚体中的骨骼肌生成。β1基因敲除嵌合小鼠的躯干和四肢含有由正常和成肌细胞β1基因敲除的细胞组成的肌肉组织，这表明所有肌节亚系在缺乏β1整合素表达的情况下都能形成、迁移到其外周靶点并融合。分别从β1基因敲除嵌合胚胎和嵌合新生小鼠中分离得到的纯β1基因敲除成肌细胞和卫星细胞群体能够在体外分化并融合成多核肌管。正常和成肌细胞β1基因敲除细胞之间的定量和定性比较显示，它们在终末分化和融合能力上没有明显差异。此外，β1基因敲除的肌管形成了与野生型对照无明显差异的肌节。当正常和β1基因敲除的胚胎干细胞分化为类胚体时，它们含有具有正常肌节和正常肌小节成分沉积的完全分化的肌管。然而，β1基因敲除的肌管形成延迟，且在β1基因敲除的类胚体中比在野生型对照中效率更低。正常和β1基因敲除的肌管顶端αv整合素亚基的高表达表明，β1整合素的缺乏并未导致含αv受体的显著重新分布。
