Embryology Unit, Children's Medical Research Institute, Westmead, NSW 2145, Australia
School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia.
Development. 2019 Apr 5;146(7):dev172858. doi: 10.1242/dev.172858.
During embryogenesis, the stringent regulation of Wnt activity is crucial for the morphogenesis of the head and brain. The loss of function of the Wnt inhibitor Dkk1 results in elevated Wnt activity, loss of ectoderm lineage attributes from the anterior epiblast, and the posteriorisation of anterior germ layer tissue towards the mesendoderm. The modulation of Wnt signalling may therefore be crucial for the allocation of epiblast cells to ectoderm progenitors during gastrulation. To test this hypothesis, we examined the lineage characteristics of epiblast stem cells (EpiSCs) that were derived and maintained under different signalling conditions. We showed that suppression of Wnt activity enhanced the ectoderm propensity of the EpiSCs. Neuroectoderm differentiation of these EpiSCs was further empowered by the robust re-activation of Wnt activity. Therefore, during gastrulation, the tuning of the signalling activities that mediate mesendoderm differentiation is instrumental for the acquisition of ectoderm potency in the epiblast.
在胚胎发生过程中，Wnt 活性的严格调节对于头部和大脑的形态发生至关重要。Wnt 抑制剂 Dkk1 的功能丧失会导致 Wnt 活性升高，前外胚层失去外胚层谱系特征，并使前胚层组织向中胚层-内胚层方向后端化。因此，Wnt 信号的调节对于在原肠胚形成过程中胚胎外细胞向外胚层祖细胞的分配可能至关重要。为了验证这一假设，我们检查了在不同信号条件下衍生和维持的胚胎外干细胞 (EpiSCs) 的谱系特征。我们表明，抑制 Wnt 活性增强了 EpiSCs 的外胚层倾向。通过强烈重新激活 Wnt 活性，进一步增强了这些 EpiSCs 的神经外胚层分化。因此，在原肠胚形成过程中，调节介导中胚层-内胚层分化的信号活性对于胚胎外细胞获得外胚层潜能至关重要。
