Department of Animal Sciences, University of Illinois, Urbana, IL 61801, USA.
Dev Biol. 2011 Jan 15;349(2):417-26. doi: 10.1016/j.ydbio.2010.10.010. Epub 2010 Oct 20.
Over the first 4 days of their life, primordial germ cells invade the endoderm, migrate into and through the developing hindgut, and traverse to the genital ridge where they cluster and ultimately inhabit the nascent gonad. Specific signal-receptor combinations between primordial germ cells and their immediate environment establish successful migration and colonization. Here we demonstrate that disruption of a cluster of six genes on murine chromosome 8, as exemplified by the Fused Toes (Ft) mutant mouse model, results in severely decreased numbers of primordial germ cells within the early gonad. Primordial germ cell migration appeared normal within Ft mutant embryos; however, germ cell counts progressively decreased during this time. Although no difference in apoptosis was detected, we report a critical decrease in primordial germ cell proliferation by E12.5. The six genes within the Ft locus include the IrxB cluster (Irx3, -5, -6), Fts, Ftm, and Fto, of which only Ftm, Fto, and Fts are expressed in primordial germ cells of the early gonad. From these studies, we have discovered that the Ft locus on mouse chromosome 8 is associated with cell cycle deficits within the primordial germ cell population that initiates just before translocation into the genital ridge.
在生命的头 4 天里，原始生殖细胞侵入内胚层，迁移到并穿过正在发育的后肠，并迁移到生殖嵴，在那里它们聚集并最终栖息在新生的性腺中。原始生殖细胞与其周围环境之间的特定信号-受体组合建立了成功的迁移和定植。在这里，我们证明了以融合脚趾（Ft）突变体小鼠模型为例的小鼠 8 号染色体上的一组六个基因的破坏，导致早期性腺中的原始生殖细胞数量严重减少。在 Ft 突变体胚胎中，原始生殖细胞的迁移似乎正常；然而，在此期间，生殖细胞计数逐渐减少。尽管没有检测到凋亡的差异，但我们报告说，E12.5 时原始生殖细胞的增殖出现了关键下降。Ft 基因座内的六个基因包括 IrxB 簇（Irx3、-5、-6）、Fts、Ftm 和 Fto，其中只有 Ftm、Fto 和 Fts 在早期性腺的原始生殖细胞中表达。从这些研究中，我们发现小鼠 8 号染色体上的 Ft 基因座与原始生殖细胞群中的细胞周期缺陷有关，这些缺陷在向生殖嵴转移之前就开始了。
