Abstract:
The SRY HMG box transcription factor Sox21 plays multiple critical roles in neurogenesis, with its function dependent on concentration and developmental stage. In the allotetraploid Xenopus laevis, there are two homeologs of sox21, namely sox21.S and sox21.L. Previous studies focused on Sox21.S, but its amino acid sequence is divergent, lacking conserved poly-A stretches and bearing more similarity with ancestral homologs. In contrast, Sox21.L shares higher sequence similarity with mouse and chick Sox21. To determine if Sox21.S and Sox21.L have distinct functions, we conducted gain and loss-of-function studies in Xenopus embryos. Our studies revealed that Sox21.S and Sox21.L are functionally redundant, but Sox21.L is more effective at driving changes than Sox21.S. These results also support our earlier findings in ectodermal explants, demonstrating that Sox21 function is dose-dependent. While Sox21 is necessary for primary neuron formation, high levels prevent their formation. Strikingly, these proteins autoregulate, with high levels of Sox21.L reducing sox21.S and sox21.L mRNA levels, and decreased Sox21.S promoting increased expression of sox21.L. Our findings shed light on the intricate concentration-dependent roles of Sox21 homeologs in Xenopus neurogenesis.
摘要:
SRYHMG盒转录因子Sox21在神经发生中起着多种关键作用,其功能取决于浓度和发育阶段。在同种四倍体非洲爪狼中,有两个同源的sox21,即sox21。S和sox21。L.以前的研究集中在Sox21。S,但是它的氨基酸序列是不同的,缺乏保守的poly-A延伸,并且与祖先同源物具有更多相似性。相比之下,Sox21.L与小鼠和小鸡Sox21具有更高的序列相似性。确定Sox21。S和Sox21。L有不同的功能,我们对非洲爪狼胚胎进行了功能增加和功能丧失研究.我们的研究表明,Sox21。S和Sox21。L在功能上是多余的,但是Sox21.L在驱动变化方面比Sox21更有效。S.这些结果也支持我们在外胚层外植体中的早期发现,证明Sox21功能是剂量依赖性的。虽然Sox21是初级神经元形成所必需的,高水平阻止其形成。引人注目的是,这些蛋白质自我调节,高水平的Sox21。L还原sox21。S和sox21。LmRNA水平,并减少Sox21。S促进sox21的表达增加。L.我们的发现揭示了Sox21同源物在非洲爪狼神经发生中复杂的浓度依赖性作用。