Teegala Sushma, Chauhan Riddhi, Lei Emily, Weinstein Daniel C
Department of Biology, The Graduate Center, City University of New York, New York.
Department of Biology, Queens College, City University of New York, Flushing, New York.
Dev Dyn. 2018 Jul;247(7):903-913. doi: 10.1002/dvdy.24633. Epub 2018 May 4.
T-box family proteins are DNA-binding transcriptional regulators that play crucial roles during germ layer formation in the early vertebrate embryo. Well-characterized members of this family, including the transcriptional activators Brachyury and VegT, are essential for the proper formation of mesoderm and endoderm, respectively. To date, T-box proteins have not been shown to play a role in the promotion of the third primary germ layer, ectoderm.
Here, we report that the T-box factor Tbx2 is both sufficient and necessary for ectodermal differentiation in the frog Xenopus laevis. Tbx2 is expressed zygotically in the presumptive ectoderm, during blastula and gastrula stages. Ectopic expression of Tbx2 represses mesoderm and endoderm, while loss of Tbx2 leads to inappropriate expression of mesoderm- and endoderm-specific genes in the region fated to give rise to ectoderm. Misexpression of Tbx2 also promotes neural tissue in animal cap explants, suggesting that Tbx2 plays a role in both the establishment of ectodermal fate and its dorsoventral patterning.
Our studies demonstrate that Tbx2 functions as a transcriptional repressor during germ layer formation, and suggest that this activity is mediated in part through repression of target genes that are stimulated, in the mesendoderm, by transactivating T-box proteins. Taken together, our results point to a critical role for Tbx2 in limiting the potency of blastula-stage progenitor cells during vertebrate germ layer differentiation. Developmental Dynamics 247:903-913, 2018. © 2018 Wiley Periodicals, Inc.
T 盒家族蛋白是 DNA 结合转录调节因子,在脊椎动物胚胎早期的胚层形成过程中发挥关键作用。该家族中特征明确的成员,包括转录激活因子短尾型蛋白(Brachyury)和 VegT,分别对中胚层和内胚层的正常形成至关重要。迄今为止,尚未发现 T 盒蛋白在促进第三初级胚层即外胚层的形成中发挥作用。
在此,我们报告 T 盒因子 Tbx2 在非洲爪蟾的外胚层分化中既是充分条件也是必要条件。Tbx2 在囊胚期和原肠胚期的预定外胚层中合子表达。Tbx2 的异位表达抑制中胚层和内胚层,而 Tbx2 的缺失导致在注定产生外胚层的区域中中胚层和内胚层特异性基因的不适当表达。Tbx2 的错误表达也促进动物帽外植体中的神经组织,这表明 Tbx2 在建立外胚层命运及其背腹模式中均发挥作用。
我们的研究表明,Tbx2 在胚层形成过程中作为转录抑制因子发挥作用,并表明这种活性部分是通过抑制在中内胚层中由反式激活 T盒蛋白刺激的靶基因来介导的。综上所述,我们的结果表明 Tbx2 在脊椎动物胚层分化过程中对限制囊胚期祖细胞的潜能起着关键作用。《发育动力学》247:903 - 913,2018 年。© 2018 威利期刊公司