The role of SF/HGF and c-Met in the development of skeletal muscle.

The role of SF/HGF and c-Met in the development of skeletal muscle.
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SF/HGF 和 c-Met 在骨骼肌发育中的作用。

DOI:
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发表时间:
1999
期刊:
影响因子:
4.6
通讯作者:
C. Birchmeier
C. Birchmeier
中科院分区:
生物学2区
文献类型:
--
作者:
S. Dietrich;F. Abou;Henning Brohmann;F. Bladt;E. Sonnenberg‐Riethmacher;T. Yamaai;A. Lumsden;B. Brand;C. Birchmeier

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轴下骨骼肌由皮肌节的侧唇产生的迁移性和非迁移性前体细胞发育而成。以前的工作表明,迁移前体的形成需要c-Met和SF/HGF基因。我们在这里表明,在缺乏c-Met或SF/HGF的小鼠中,皮肌节的初始发育适当进行,皮肌节中细胞的生长和存活不受影响。迁移的前体也被正确地指定,监测Lbx 1的表达。然而,这些细胞保持聚集并且不能进行长距离迁移。我们的结论是,平行但独立的线索收敛于迁移hypaxial前体在dermomyotomal唇后,他们奠定了:由SF/HGF,控制前体的移民,和一个尚未确定的信号,控制Lbx 1的信号。SF/HGF和c-Met以旁分泌方式控制迁移,迁移细胞仅与靠近SF/HGF表达细胞的体节分离。在长距离迁移过程中,似乎需要延长的受体-配体相互作用,因为SF/HGF沿着迁移的肌原性祖细胞的路线和靶位点表达。缺乏c-Met的小鼠在妊娠的第二部分由于胎盘缺陷而死亡。通过四倍体(野生型)和二倍体(c-Met-/-)桑椹胚的聚集来挽救胎盘缺陷,允许c-Met突变动物的发育。他们缺乏来自迁移前体细胞的肌肉群,但显示其他正常的骨骼肌组织。
Hypaxial skeletal muscles develop from migratory and non-migratory precursor cells that are generated by the lateral lip of the dermomyotome. Previous work shows that the formation of migratory precursors requires the c-Met and SF/HGF genes. We show here that in mice lacking c-Met or SF/HGF, the initial development of the dermomyotome proceeds appropriately and growth and survival of cells in the dermomyotome are not affected. Migratory precursors are also correctly specified, as monitored by the expression of Lbx1. However, these cells remain aggregated and fail to take up long range migration. We conclude that parallel but independent cues converge on the migratory hypaxial precursors in the dermomyotomal lip after they are laid down: a signal given by SF/HGF that controls the emigration of the precursors, and an as yet unidentified signal that controls Lbx1. SF/HGF and c-Met act in a paracrine manner to control emigration, and migratory cells only dissociate from somites located close to SF/HGF-expressing cells. During long range migration, prolonged receptor-ligand-interaction appears to be required, as SF/HGF is expressed both along the routes and at the target sites of migratory myogenic progenitors. Mice that lack c-Met die during the second part of gestation due to a placental defect. Rescue of the placental defect by aggregation of tetraploid (wild type) and diploid (c-Met-/-) morulae allows development of c-Met mutant animals to term. They lack muscle groups that derive from migratory precursor cells, but display otherwise normal skeletal musculature.
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