Developmental Cell ( IF 10.7 ) Pub Date : 2019-01-17 , DOI: 10.1016/j.devcel.2018.12.004 Rita Aires , Luisa de Lemos , Ana Nóvoa , Arnon Dias Jurberg , Bénédicte Mascrez , Denis Duboule , Moisés Mallo
During the trunk-to-tail transition, axial progenitors relocate from the epiblast to the tail bud. Here, we show that this process entails a major regulatory switch, bringing tail bud progenitors under Gdf11 signaling control. Gdf11 mutant embryos have an increased number of such progenitors that favor neural differentiation routes, resulting in a dramatic expansion of the neural tube. Moreover, inhibition of Gdf11 signaling recovers the proliferation ability of these progenitors when cultured in vitro. Tail bud progenitor growth is independent of Oct4, relying instead on Lin28 activity. Gdf11 signaling eventually activates Hox genes of paralog group 13, which halt expansion of these progenitors, at least in part, by down-regulating Lin28 genes. Our results uncover a genetic network involving Gdf11, Lin28, and Hox13 genes controlling axial progenitor activity in the tail bud.
中文翻译:
尾芽祖细胞活动依赖于包含Gdf11,Lin28和Hox13基因的网络
在躯干到尾巴的过渡过程中,轴向祖细胞从上皮细胞移至尾芽。在这里,我们显示此过程需要一个主要的调节开关,使尾芽祖细胞处于Gdf11信号控制之下。Gdf11突变体胚胎的此类祖细胞数量增加,有利于神经分化途径,导致神经管急剧膨胀。此外,在体外培养时,抑制Gdf11信号可恢复这些祖细胞的增殖能力。尾芽祖细胞的生长不依赖于Oct4,而是依赖于Lin28的活性。Gdf11信号最终激活Hox旁系同源物13的基因,至少部分地通过下调Lin28基因来阻止这些祖细胞的扩增。我们的研究结果揭示了涉及Gdf11,Lin28和Hox13基因的遗传网络,这些基因控制着尾芽中的轴向祖细胞活性。