Buckingham Margaret, Bajard Lola, Daubas Philippe, Esner Milan, Lagha Mounia, Relaix Frédéric, Rocancourt Didier
Department of Developmental Biology, CNRS URA2578, Pasteur Institute, 25 rue du Dr Roux, 75015, Paris, France.
Anat Embryol (Berl). 2006 Dec;211 Suppl 1:51-6. doi: 10.1007/s00429-006-0122-0. Epub 2006 Oct 13.
The transcription factors Pax3 and Pax7 are important regulators of myogenic cell fate, as demonstrated by genetic manipulations in the mouse embryo. Pax3 lies genetically upstream of MyoD and has also been shown recently to directly control Myf5 transcription in derivatives of the hypaxial somite, where it also plays an important role in ensuring cell survival. Both Pax3 and Pax7 are expressed in myogenic progenitor cells derived from the central dermomyotome that make a major contribution to skeletal muscle growth. In Pax3/Pax7 double mutants, the myogenic determination genes, Myf5 and MyoD, are not activated in these cells which become incorporated into other tissues or die. This again demonstrates the dual function of Pax factors in regulating the entry of progenitor cells into the myogenic programme and in ensuring their survival. Pax3 expression marks cells in the dermomyotome that either become myogenic or downregulate Pax3 and assume another cell fate. The latter include the smooth muscle cells of the dorsal aorta that share a common clonal origin with the skeletal muscle of the myotome, thus illustrating the initial multipotency of Pax3 expressing cells.
转录因子Pax3和Pax7是成肌细胞命运的重要调节因子,这在小鼠胚胎的基因操作中得到了证实。Pax3在基因上位于MyoD的上游,最近还被证明能直接控制轴下肌节衍生物中Myf5的转录,在确保细胞存活方面也发挥着重要作用。Pax3和Pax7都在源自中央皮肌节的成肌祖细胞中表达,这些祖细胞对骨骼肌生长有重要贡献。在Pax3/Pax7双突变体中,成肌决定基因Myf5和MyoD在这些细胞中未被激活,这些细胞会融入其他组织或死亡。这再次证明了Pax因子在调节祖细胞进入成肌程序以及确保其存活方面的双重功能。Pax3的表达标记了皮肌节中要么成为成肌细胞,要么下调Pax3并承担另一种细胞命运的细胞。后者包括背主动脉的平滑肌细胞,它们与肌节的骨骼肌有共同的克隆起源,从而说明了表达Pax3的细胞最初的多能性。