Institute of Biochemistry, University of Ulm, 89081, Ulm, Germany.
Dev Growth Differ. 2012 Sep;54(7):702-16. doi: 10.1111/j.1440-169X.2012.01371.x. Epub 2012 Sep 7.
POU-V class proteins like Oct4 are crucial for keeping cells in an undifferentiated state. An Oct4 homologue in Xenopus laevis, Oct25, peaks in expression during early gastrulation, when many cells are still uncommitted. Nevertheless, extensive morphogenesis is taking place in all germ layers at that time. Phenotypical analysis of embryos with Oct25 overexpression revealed morphogenesis defects, beginning during early gastrulation and resulting in spina-bifida-like axial defects. Analysis of marker genes and different morphogenesis assays show inhibitory effects on convergence and extension and on mesoderm internalization. On a cellular level, cell-cell adhesion is reduced. On a molecular level, Oct25 overexpression activates expression of PAPC, a functional inhibitor of the cell adhesion molecule EP/C-cadherin. Intriguingly, Oct25 effects on cell-cell adhesion can be restored by overexpression of EP/C-cadherin or by inhibition of the PAPC function. Thus, Oct25 affects morphogenesis via activation of PAPC expression and subsequent functional inhibition of EP/C-cadherin.
POU-V 类蛋白,如 Oct4,对于维持细胞未分化状态至关重要。非洲爪蟾的 Oct4 同源物 Oct25 在早期原肠胚形成时表达达到高峰,此时许多细胞仍然没有定型。然而,此时所有胚层都在进行广泛的形态发生。对过表达 Oct25 的胚胎进行表型分析显示,形态发生缺陷始于早期原肠胚形成期,并导致脊柱裂样的轴向缺陷。对标记基因和不同形态发生测定的分析表明,它对会聚延伸和中胚层内化具有抑制作用。在细胞水平上,细胞间的黏附减少。在分子水平上,Oct25 的过表达激活了 PAPC 的表达,PAPC 是细胞黏附分子 EP/C-钙黏蛋白的功能抑制剂。有趣的是,过表达 EP/C-钙黏蛋白或抑制 PAPC 功能可以恢复 Oct25 对细胞间黏附的影响。因此,Oct25 通过激活 PAPC 的表达并随后抑制 EP/C-钙黏蛋白的功能来影响形态发生。