Six and Eya expression during human somitogenesis and MyoD gene family activation

Six and Eya expression during human somitogenesis and MyoD gene family activation
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DOI:
10.1023/a:1020990825644
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发表时间:
2002-04-01
影响因子:
2.7
通讯作者:
Maire, P
Maire, P
中科院分区:
生物学3区
文献类型:
--
作者:
Fougerousse, F;Durand, M;Maire, P

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本报告描述了几个肌源性决定基因在人类胚胎发育过程中的表达特征。这些数据来自发育3到8周的人类胚胎的轴向结构和肢芽。利用原位杂交法检测Pax3和MyoD基因家族的mRNAs,免疫组织化学跟踪Six和Eya蛋白的积累,我们已经能够建立这些基因产物积累的年表。与小鼠一样,在3周龄胚胎的肌瘤中首先检测到Pax3和Myf5的转录本,其次是肌生成素的表达。在早期肌节中,MyoD似乎在Myf5、mygenin和MRF4之后被很好地激活,而在肢芽肌中,这四种mRNAs的存在从6周开始伴随而来。SIX1、Six4和Six5同源蛋白的检测晚于Myf5的激活。这六种同源蛋白首次在表达肌生成素的细胞的胞浆中被观察到。在发育的后期,SIX1和Six5,而不是Six4,被转位到肌原细胞的核中,伴随着MyHCemb的表达。在生肌素阳性细胞中也检测到EYA1和EYA2蛋白,但它们的蓄积延迟,且主要为胞质。这些结果排除了Myf5、Mygenin和MRF4的早期激活是由Six和Eya蛋白控制的,而Six和Eya蛋白可能参与了成肌分化的后期步骤。
This report describes the characterisation of the expression pro le of several myogenic determination genes during human embryogenesis. The data were obtained from axial structures and limb buds of human embryos aged between 3 and 8 weeks of development. Using in situ hybridisation to detect Pax3 and MyoD gene family mRNAs, and immunochemistry to follow Six and Eya protein accumulation, we have been able to establish the chronology of accumulation of these gene products. As in mouse, the first transcripts detected in myotomes of 3 week-old embryos are Pax3 and Myf5, followed by the expression of myogenin. MyoD appears to be activated well after Myf5, myogenin and MRF4 in the early myotome, whereas, in limb bud muscles, the presence of all four of these mRNAs is concomitant from 6 weeks. Six1, Six4 and Six5 homeoproteins are detected later than Myf5 activation. These Six homeoproteins are first observed in the cytoplasm of myogenin expressing cells. At later stages of development, Six1 and Six5, but not Six4, are translocated into the nuclei of myogenic cells, concomitantly with MyHCemb expression. Eya1 and Eya2 proteins, potential Six cofactors, were also detected in myogenin positive cells, but their accumulation was delayed and was mainly cytoplasmic. These results preclude that early activation of Myf5, myogenin and MRF4 is under the control of Six and Eya proteins, while Six and Eya proteins would be involved in later steps of myogenic differentiation.