Abstract:
SoxB1 transcription factors (Sox2/3) are well known for their role in early neural fate specification in the embryo, but little is known about functional roles for SoxB1 factors in non-neural ectodermal cell types, such as the neural plate border (NPB). Using Xenopus laevis, we set out to determine whether SoxB1 transcription factors have a regulatory function in NPB formation. Here, we show that SoxB1 factors are necessary for NPB formation, and that prolonged SoxB1 factor activity blocks the transition from a NPB to a neural crest state. Using ChIP-seq, we demonstrate that Sox3 is enriched upstream of NPB genes in early NPB cells and in blastula stem cells. Depletion of SoxB1 factors in blastula stem cells results in downregulation of NPB genes. Finally, we identify Pou5f3 factors as potential Sox3 partners in regulating the formation of the NPB and show that their combined activity is needed for normal NPB gene expression. Together, these data identify a role for SoxB1 factors in the establishment and maintenance of the NPB, in part through partnership with Pou5f3 factors.
摘要:
SoxB1转录因子(Sox2/3)因其在胚胎早期神经命运规范中的作用而闻名,但对SoxB1因子在非神经外胚层细胞类型中的功能作用知之甚少,如神经板边界(NPB)。使用非洲爪狼,我们着手确定SoxB1转录因子是否在NPB形成中具有调节功能。在这里,我们证明SoxB1因子是NPB形成所必需的,并且延长的SoxB1因子活性阻止了从NPB到神经c状态的转变。使用ChIP-seq我们证明Sox3在早期NPB细胞和囊胚干细胞中富集在NPB基因的上游。囊胚干细胞中SoxB1因子的耗尽导致NPB基因的下调。最后,我们将Pou5f3因子鉴定为调节NPB形成的潜在Sox3伴侣,并显示正常NPB基因表达需要它们的联合活性。一起,这些数据确定了SoxB1因子在NPB的建立和维持中的新作用,部分是通过与Pou5f3因素的合作。