Yoshida Megumi, Uchikawa Masanori, Rizzoti Karine, Lovell-Badge Robin, Takemoto Tatsuya, Kondoh Hisato
Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
National Institute for Medical Research, London NW7 1AA, UK.
Mech Dev. 2014 May;132:59-68. doi: 10.1016/j.mod.2014.01.003. Epub 2014 Feb 6.
High expression of the B1 Sox genes, Sox2 and Sox3, is associated with the development of definitive neural primordia, the neural plates, in early stage embryos. However, in the caudal lateral epiblast (CLE) where axial stem cells reside, Sox2 and Sox3 are expressed at low levels, together with Brachyury. Because axial stem cells are the bipotential precursors of the neural plate and paraxial mesoderm, we investigated the possibility that low-level B1 Sox expression in CLE may regulate the fate of axial stem cells. We combined the genetic conditions of Sox3-null and Sox2 N1 enhancer homozygous deletion (Sox2(ΔN1/ΔN1)) to decrease B1 Sox expression in CLE. At 5-7 somite stages of mouse embryogenesis, these genetic manipulations caused approximately 30% higher production of paraxial mesodermal precursors, resulting in the development of larger somites. Analysis of mitotic cell populations suggested that decrease of B1 Sox expression in CLE does not activate cell proliferation but promotes cell migration into the mesodermal compartment. Thus, the low-level B1 Sox expression in CLE regulates axial stem cells to adjust the production of paraxial mesoderm precursors to an appropriate level.
B1 Sox基因Sox2和Sox3的高表达与早期胚胎中确定的神经原基即神经板的发育相关。然而，在轴向干细胞所在的尾侧外侧上胚层（CLE）中，Sox2和Sox3与Brachyury一起低水平表达。由于轴向干细胞是神经板和近轴中胚层的双能前体，我们研究了CLE中低水平的B1 Sox表达可能调节轴向干细胞命运的可能性。我们结合了Sox3基因敲除和Sox2 N1增强子纯合缺失（Sox2(ΔN1/ΔN1)）的遗传条件，以降低CLE中B1 Sox的表达。在小鼠胚胎发育的5至7体节阶段，这些基因操作使近轴中胚层前体的产生增加了约30%，导致更大的体节发育。对有丝分裂细胞群体的分析表明，CLE中B1 Sox表达的降低不会激活细胞增殖，但会促进细胞迁移到中胚层区室。因此，CLE中低水平的B1 Sox表达调节轴向干细胞，以将近轴中胚层前体的产生调整到适当水平。
