Membrane-bound steel factor maintains a high local concentration for mouse primordial germ cell motility, and defines the region of their migration.
Membrane-bound steel factor maintains a high local concentration for mouse primordial germ cell motility, and defines the region of their migration.
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DOI：
10.1371/journal.pone.0025984
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wylie C
中科院分区：
文献类型：
--
作者：
Gu Y;Runyan C;Shoemaker A;Surani MA;Wylie C
Steel因子是小鼠Steel基因座的蛋白产物，是原始生殖细胞群体的多功能信号。我们以前已经表明，它的表达伴随着生殖细胞迁移到性腺，形成一个“旅行小生境”，控制他们的生存，运动和增殖。在这里，我们表明，这些功能分布在选择性剪接的膜结合和可溶性形式的钢因子。生殖细胞通常从E7.5迁移到E11.5，当它们在胚胎性腺中聚集在一起时。Steel-dickie突变体胚胎的电影分析显示，在E7.5时，生殖细胞不能正常迁移，并在尿囊基部发生“过早聚集”。生存和运动方向不受影响。添加过量的可溶性钢因子Steel-dickie胚胎挽救生殖细胞的运动性，并在体外添加钢因子的生殖细胞表明，需要四倍高的剂量，以增加运动性，相比生存。这些数据表明，可溶性钢因子足以使生殖细胞存活，并表明膜结合形式提供了更高的局部浓度的钢因子，其控制生殖细胞运动性和聚集之间的平衡。通过向E11.5胚胎的切片培养物中加入过量的可溶性Steel因子来测试这一假设，此时迁移通常停止，并且生殖细胞聚集。这逆转了聚集过程，并导致生殖细胞的运动性增加。我们的结论是，这两种形式的钢因子控制不同方面的生殖细胞的行为，和膜结合的钢因子控制生殖细胞的运动在一个“运动生态位”，通过胚胎与生殖细胞。从这个生态位的逃逸导致运动停止和异位生殖细胞凋亡死亡。
Steel factor, the protein product of the Steel locus in the mouse, is a multifunctional signal for the primordial germ cell population. We have shown previously that its expression accompanies the germ cells during migration to the gonads, forming a “travelling niche” that controls their survival, motility, and proliferation. Here we show that these functions are distributed between the alternatively spliced membrane-bound and soluble forms of Steel factor. The germ cells normally migrate as individuals from E7.5 to E11.5, when they aggregate together in the embryonic gonads. Movie analysis of Steel-dickie mutant embryos, which make only the soluble form, at E7.5, showed that the germ cells fail to migrate normally, and undergo “premature aggregation” in the base of the allantois. Survival and directionality of movement is not affected. Addition of excess soluble Steel factor to Steel-dickie embryos rescued germ cell motility, and addition of Steel factor to germ cells in vitro showed that a fourfold higher dose was required to increase motility, compared to survival. These data show that soluble Steel factor is sufficient for germ cell survival, and suggest that the membrane-bound form provides a higher local concentration of Steel factor that controls the balance between germ cell motility and aggregation. This hypothesis was tested by addition of excess soluble Steel factor to slice cultures of E11.5 embryos, when migration usually ceases, and the germ cells aggregate. This reversed the aggregation process, and caused increased motility of the germ cells. We conclude that the two forms of Steel factor control different aspects of germ cell behavior, and that membrane-bound Steel factor controls germ cell motility within a “motility niche” that moves through the embryo with the germ cells. Escape from this niche causes cessation of motility and death by apoptosis of the ectopic germ cells.
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DOI：
10.1073/pnas.88.11.4671
发表时间：
1991-06-01
影响因子：
11.1
作者：
BRANNAN, CI;LYMAN, SD;COPELAND, NG
通讯作者：
COPELAND, NG
影响因子：
3.6
作者：
Zama, AM;Hudson, FP;Bedell, MA
通讯作者：
Bedell, MA
影响因子：
64.8
作者：
MATSUI, Y;TOKSOZ, D;HOGAN, BLM
通讯作者：
HOGAN, BLM
影响因子：
1.8
作者：
Friel, J;Itoh, K;Ostertag, W
通讯作者：
Ostertag, W
影响因子：
64.8
作者：
GODIN, I;DEED, R;WYLIE, CC
通讯作者：
WYLIE, CC