Gene regulatory network governing the neural plate development from the epiblast

我们研究了神经板（神经前体）从泛体细胞组织前体外胚层衍生的调控机制。我们在培养条件下利用突变小鼠胚胎和外胚层干细胞。以Sox2 N2增强子活性为标志的前神经板是通过转录因子的协同作用直接从外胚层衍生而来的，这些转录因子促进神经发育，但抑制所有非神经谱系的发育。相比之下，以Sox2 N1增强子活性为标志的后神经板通过称为“轴向干细胞”的神经-中胚层双电位前体发育。依赖tbx6的N1增强子抑制是中胚层发育所必需的。这些新发现修订了体细胞谱系分离的经典观点，其中胚层分离被认为是必不可少的第一步。

We investigated the regulatory mechanisms that underlie the derivation of the neural plates (neural precursors) from the pan-somatic tissue precursor epiblast. We took advantage of mutant mouse embryos and epiblast stem cells under culture conditions.The anterior neural plate, as marked by Sox2 N2 enhancer activity, was derived directly from the epiblast through the cooperative action of transcription factors that promote neural development but repress the development of all non-neural lineages. By contrast, the posterior neural plate, as marked by Sox2 N1 enhancer activity, developed through neuro-mesodermal bipotential precursors named "axial stem cells". Tbx6-dependent repression of the N1 enhancer was required for mesodermal development. These new findings revise the classical view of somatic cell lineage separation, where germ layer separation was assumed to be the essential first step.