Pax3 functions in cell survival and in pax7 regulation.
Pax3 functions in cell survival and in pax7 regulation.
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发表时间：
1999-04
期刊：
影响因子：
4.6
通讯作者：
A. Borycki;Jun Li;F. Jin;C. Emerson;Jonathan A. Epstein
中科院分区：
文献类型：
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作者：
A. Borycki;Jun Li;F. Jin;C. Emerson;Jonathan A. Epstein
在发育中的脊椎动物胚胎中，Pax3在神经管和形成骨骼肌的近轴中胚层中表达。Pax3突变导致肌肉和神经管缺陷；此外，在肌肉发育的早期，Pax3对于生肌决定基因MyoD的正确激活是必不可少的，而PAX3染色体易位导致肌肉肿瘤，这为Pax3在肌肉发生中具有不同的功能提供了证据。为了研究Pax3在发育中的特定功能，我们检测了野生型和Pax3突变型(Splotch)小鼠胚胎发育中的中胚层、体节和神经管中的细胞存活和基因表达。Pax3的表达被反义寡核苷酸阻断后，可通过神经管/脊索和表面外胚层的信号显著抑制MyoD的激活，并伴随着细胞程序性死亡的显著增加。在Pax3突变体(Splotch)胚胎中，MyoD在下轴体节中正常激活，但表达MyoD的细胞紊乱，在新形成的体节中普遍存在凋亡，但在神经管或成熟体节中不存在。在维持细胞存活的神经管和体节区域，密切相关的Pax7基因上调，其表达扩展到背侧神经管和体节，通常在那里表达Pax3。这些结果表明，在神经管和体节发育过程中，Pax3在体细胞中胚层MyoD的激活和抑制细胞凋亡以及Pax7的抑制方面具有互补功能。
In developing vertebrate embryos, Pax3 is expressed in the neural tube and in the paraxial mesoderm that gives rise to skeletal muscles. Pax3 mutants develop muscular and neural tube defects; furthermore, Pax3 is essential for the proper activation of the myogenic determination factor gene, MyoD, during early muscle development and PAX3 chromosomal translocations result in muscle tumors, providing evidence that Pax3 has diverse functions in myogenesis. To investigate the specific functions of Pax3 in development, we have examined cell survival and gene expression in presomitic mesoderm, somites and neural tube of developing wild-type and Pax3 mutant (Splotch) mouse embryos. Disruption of Pax3 expression by antisense oligonucleotides significantly impairs MyoD activation by signals from neural tube/notochord and surface ectoderm in cultured presomitic mesoderm (PSM), and is accompanied by a marked increase in programmed cell death. In Pax3 mutant (Splotch) embryos, MyoD is activated normally in the hypaxial somite, but MyoD-expressing cells are disorganized and apoptosis is prevalent in newly formed somites, but not in the neural tube or mature somites. In neural tube and somite regions where cell survival is maintained, the closely related Pax7 gene is upregulated, and its expression becomes expanded into the dorsal neural tube and somites, where Pax3 would normally be expressed. These results establish that Pax3 has complementary functions in MyoD activation and inhibition of apoptosis in the somitic mesoderm and in repression of Pax7 during neural tube and somite development.