Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression during myogenesis in the mouse embryo
Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression during myogenesis in the mouse embryo
复制标题
DOI：
10.1242/dev.01773
复制
发表时间：
2005-05-01
期刊：
影响因子：
4.6
通讯作者：
Maire, P
中科院分区：
文献类型：
--
作者：
Grifone, R;Demignon, J;Maire, P
在哺乳动物中，Six5、Six4和Six1基因在小鼠肌肉发生期间共表达。Six4和Six5单基因敲除（KO）小鼠没有发育缺陷，而Six1 KO小鼠在出生时死亡并显示多器官发育缺陷。我们已经产生了Six1Six4双KO小鼠，并显示出先前报道的单Six1 KO的表型恶化。Six1Six4双KO小鼠的特征在于严重的颅面和肋骨缺陷以及全身肌肉发育不全。在肢芽水平，Six1和Six4 homogenes通过控制Pax3基因表达控制肌细胞分层和从体节迁移的早期步骤。在其迁移途径受损，体节腹外侧皮肌节的细胞改道，失去其身份，并通过凋亡死亡。在interlimb水平，epaxial Met的表达被废除，而它被保存在Pax3缺陷的胚胎。在肌节内，Six1和Six4的缺失损害了生肌调节因子myogenin和Myod1的表达，并且Mrf4的表达变得不可检测。Myf5的表达被正确地启动，但被限制在每个体节的尾部区域。在Six1Six4胚胎中，巩膜轴的早期联会表达减少，而Fgfr 4和Fgf 8而非Fgf 4和Fgf 6的肌节表达得以维持。这些结果强调了六种蛋白质在骨骼肌发生过程中发挥的不同作用。
In mammals, Six5, Six4 and Six1 genes are co-expressed during mouse myogenesis. Six4 and Six5 single knockout (KO) mice have no developmental defects, while Six1 KO mice die at birth and show multiple organ developmental defects. We have generated Six1Six4 double KO mice and show an aggravation of the phenotype previously reported for the single Six1 KO. Six1Six4 double KO mice are characterized by severe craniofacial and rib defects, and general muscle hypoplasia. At the limb bud level, Six1 and Six4 homeogenes control early steps of myogenic cell delamination and migration from the somite through the control of Pax3 gene expression. Impaired in their migratory pathway, cells of the somitic ventrolateral dermomyotome are rerouted, lose their identity and die by apoptosis. At the interlimb level, epaxial Met expression is abolished, while it is preserved in Pax3-deficient embryos. Within the myotome, absence of Six1 and Six4 impairs the expression of the myogenic regulatory factors myogenin and Myod1, and Mrf4 expression becomes undetectable. Myf5 expression is correctly initiated but becomes restricted to the caudal region of each somite. Early syndetomal expression of scleraxis is reduced in the Six1Six4 embryo, while the myotomal expression of Fgfr4 and Fgf8 but not Fgf4 and Fgf6 is maintained. These results highlight the different roles played by Six proteins during skeletal myogenesis.