Altered myogenesis in Six1-deficient mice
Altered myogenesis in Six1-deficient mice
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DOI：
10.1242/dev.00440
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发表时间：
2003-05-01
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：
Laclef, C;Hamard, G;Maire, P
在脊椎动物胚胎发生过程中，包括肌肉在内的几种组织中表达了六种同型蛋白，这表明它们可能参与了不同的分化过程。为了确定Six1基因在肌肉形成过程中的功能，我们用lacZ基因取代Six1基因的第一个外显子，构建了Six1缺陷小鼠。缺乏Six1的小鼠在出生时死亡，因为严重的肋骨畸形，并表现出广泛的肌肉发育不全，影响大部分身体肌肉，特别是某些下轴肌。Six1（-/-）胚胎的原发性肌肉发生受损，其特征是在E13.5时，大多数身体肌肉的原发性肌纤维严重减少和紊乱。虽然Myf5、MyoD和myogenin在早期Six1（-/-）胚胎的体室中正确表达，但到E11.5时，MyoD和myogenin基因在肢体芽中的激活减少和延迟。然而，这并不是肌原性前体细胞迁移到肢体芽的能力降低或缺乏Six1的成肌细胞异常凋亡的结果。因此，Six1与Pax3、cMet、Lbx1或Mox2等其他下轴决定因子不同，似乎在下轴肌分化中起着特定的作用。
Six homeoproteins are expressed in several tissues, including muscle, during vertebrate embryogenesis, suggesting that they may be involved in diverse differentiation processes. To determine the functions of the Six1 gene during myogenesis, we constructed Six1-deficient mice by replacing its first exon with the lacZ gene. Mice lacking Six1 die at birth because of severe rib malformations and show extensive muscle hypoplasia affecting most of the body muscles in particular certain hypaxial muscles. Six1(-/-) embryos have impaired primary myogenesis, characterized, at E13.5, by a severe reduction and disorganisation of primary myofibers in most body muscles. While Myf5, MyoD and myogenin are correctly expressed in the somitic compartment in early Six1(-/-) embryos, by E11.5 MyoD and myogenin gene activation is reduced and delayed in limb buds. However, this is not the consequence of a reduced ability of myogenic precursor cells to migrate into the limb buds or of an abnormal apoptosis of myoblasts lacking Six1. It appears therefore that Six1 plays a specific role in hypaxial muscle differentiation, distinct from those of other hypaxial determinants such as Pax3, cMet, Lbx1 or Mox2.