Tiedemann H, Asashima M, Grunz H, Knöchel W
Institut für Molekularbiologie und Biochemie der Freien Universtität Berlin, Arnimallee 22, D-14195 Berlin, Germany.
Dev Growth Differ. 2001 Oct;43(5):469-502. doi: 10.1046/j.1440-169x.2001.00599.x.
Mammalian embryonic stem cells can be obtained from the inner cell mass of blastocysts or from primordial germ cells. These stem cells are pluripotent and can develop into all three germ cell layers of the embryo. Somatic mammalian stem cells, derived from adult or fetal tissues, are more restricted in their developmental potency. Amphibian ectodermal and endodermal cells lose their pluripotency at the early gastrula stage. The dorsal mesoderm of the marginal zone is determined before the mid-blastula transition by factors located after cortical rotation in the marginal zone, without induction by the endoderm. Secreted maternal factors (BMP, FGF and activins), maternal receptors and maternal nuclear factors (beta-catenin, Smad and Fast proteins), which form multiprotein transcriptional complexes, act together to initiate pattern formation. Following mid-blastula transition in Xenopus laevis (Daudin) embryos, secreted nodal-related (Xnr) factors become important for endoderm and mesoderm differentiation to maintain and enhance mesoderm induction. Endoderm can be induced by high concentrations of activin (vegetalizing factor) or nodal-related factors, especially Xnr5 and Xnr6, which depend on Wnt/beta-catenin signaling and on VegT, a vegetal maternal transcription factor. Together, these and other factors regulate the equilibrium between endoderm and mesoderm development. Many genes are activated and/or repressed by more than one signaling pathway and by regulatory loops to refine the tuning of gene expression. The nodal related factors, BMP, activins and Vg1 belong to the TGF-beta superfamily. The homeogenetic neural induction by the neural plate probably reinforces neural induction and differentiation. Medical and ethical problems of future stem cell therapy are briefly discussed.
哺乳动物胚胎干细胞可从囊胚的内细胞团或原始生殖细胞中获得。这些干细胞具有多能性，可发育成胚胎的所有三个胚层。源自成年或胎儿组织的哺乳动物体细胞干细胞，其发育潜能更为受限。两栖动物的外胚层和内胚层细胞在原肠胚早期失去其多能性。边缘区的背侧中胚层在囊胚中期转变之前，由边缘区皮质旋转后定位的因子决定，无需内胚层诱导。分泌的母体因子（骨形态发生蛋白、成纤维细胞生长因子和激活素）、母体受体和母体核因子（β-连环蛋白、Smad和Fast蛋白）形成多蛋白转录复合物，共同作用启动模式形成。在非洲爪蟾胚胎囊胚中期转变之后，分泌的节点相关（Xnr）因子对于内胚层和中胚层分化以维持和增强中胚层诱导变得重要。高浓度的激活素（植物化因子）或节点相关因子，特别是Xnr5和Xnr6可诱导内胚层，它们依赖于Wnt/β-连环蛋白信号传导以及植物母体转录因子VegT。这些因子与其他因子共同调节内胚层和中胚层发育之间的平衡。许多基因被不止一条信号通路和调控环激活和/或抑制，以优化基因表达的调节。节点相关因子、骨形态发生蛋白、激活素和Vg1属于转化生长因子-β超家族。神经板的同源神经诱导可能会加强神经诱导和分化。本文简要讨论了未来干细胞治疗的医学和伦理问题。
