非洲爪蟾的Sox3激活Sox2和geminin,并间接抑制Xvent2的表达,以牺牲非神经外胚层衍生物为代价诱导神经祖细胞形成。
Xenopus Sox3 activates sox2 and geminin and indirectly represses Xvent2 expression to induce neural progenitor formation at the expense of non-neural ectodermal derivatives.
作者信息
Rogers Crystal D, Harafuji Naoe, Archer Tenley, Cunningham Doreen D, Casey Elena S
机构信息
Department of Biology, Georgetown University, Washington, DC 20057, USA.
出版信息
Mech Dev. 2009 Jan-Feb;126(1-2):42-55. doi: 10.1016/j.mod.2008.10.005. Epub 2008 Oct 17.
The SRY-related, HMG box SoxB1 transcription factors are highly homologous, evolutionarily conserved proteins that are expressed in neuroepithelial cells throughout neural development. SoxB1 genes are down-regulated as cells exit the cell-cycle to differentiate and are considered functionally redundant in maintaining neural precursor populations. However, little is known about Sox3 function and its mode of action during primary neurogenesis. Using gain and loss-of-function studies, we analyzed Sox3 function in detail in Xenopus early neural development and compared it to that of Sox2. Through these studies we identified the first targets of a SoxB1 protein during primary neurogenesis. Sox3 functions as an activator to induce expression of the early neural genes, sox2 and geminin in the absence of protein synthesis and to indirectly inhibit the Bmp target Xvent2. As a result, Sox3 increases cell proliferation, delays neurogenesis and inhibits epidermal and neural crest formation to expand the neural plate. Our studies indicate that Sox3 and 2 have many similar functions in this process including the ability to activate expression of geminin in naïve ectodermal explants. However, there are some differences; Sox3 activates the expression of sox2, while Sox2 does not activate expression of sox3 and sox3 is uniquely expressed throughout the ectoderm prior to neural induction suggesting a role in neural competence. With morpholino-mediated knockdown of Sox3, we demonstrate that it is required for induction of neural tissue by BMP inhibition. Together these data indicate that Sox3 has multiple roles in early neural development including as a factor required for nogginmediated neural induction.
与SRY相关的HMG盒SoxB1转录因子是高度同源、进化保守的蛋白质,在整个神经发育过程中的神经上皮细胞中表达。随着细胞退出细胞周期进行分化,SoxB1基因表达下调,并且在维持神经前体细胞群方面被认为功能冗余。然而,关于Sox3在初级神经发生过程中的功能及其作用模式知之甚少。我们通过功能获得和功能缺失研究,详细分析了非洲爪蟾早期神经发育中Sox3的功能,并将其与Sox2的功能进行比较。通过这些研究,我们确定了初级神经发生过程中SoxB1蛋白的首个靶标。在没有蛋白质合成的情况下,Sox3作为激活剂诱导早期神经基因sox2和geminin的表达,并间接抑制Bmp靶标Xvent2。结果,Sox3增加细胞增殖、延迟神经发生并抑制表皮和神经嵴形成,从而扩大神经板。我们的研究表明,Sox3和2在此过程中具有许多相似功能,包括在未分化的外胚层植块中激活geminin表达的能力。然而,也存在一些差异;Sox3激活sox2的表达,而Sox2不激活sox3的表达,并且在神经诱导之前Sox3在外胚层中独特表达,这表明其在神经感受态中发挥作用。通过吗啉代介导的Sox3敲低,我们证明它是BMP抑制诱导神经组织所必需的。这些数据共同表明Sox3在早期神经发育中具有多种作用,包括作为noggin介导的神经诱导所需的因子。