Eomes function is conserved between zebrafish and mouse and controls left-right organiser progenitor gene expression via interlocking feedforward loops.
Eomes function is conserved between zebrafish and mouse and controls left-right organiser progenitor gene expression via interlocking feedforward loops.
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DOI：
10.3389/fcell.2022.982477
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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T-box家族转录因子Eomesodermin(Eomesodermin)存在于所有脊椎动物中，在哺乳动物胚胎发育和免疫系统中起着许多关键作用。由于胚胎中胚层和胚外滋养层细胞谱系的缺陷，纯合子eome突变小鼠胚胎表现出早期死亡。相比之下，缺乏主要Eome同源A(Eomesa)的斑马鱼不会完全致死，可以维持下去。这表明Eome同源基因的分子功能或它们所参与的过程的分子配置存在根本差异。为了探索这些假设，我们最初分析了不同的Eome亚型在不同类型的小鼠细胞中的表达。接下来，我们将这些小鼠亚型与斑马鱼Eomesa的功能能力进行了比较。这些实验没有提供功能分化的证据。接下来，我们研究了斑马鱼Eomesa和其他T-box家族成员在早期发育中表达的功能，以及它的类似物Eomesb。虽然Eome是Tbr1亚家族的成员，但我们发现了与Tbx6亚家族成员Tbx16功能冗余的证据，已知Tbx16在真核生物中缺失。然而，Tbx16似乎没有与Eomesa辅助因子Mixl1和Gata5协同作用。最后，我们分析了Eomesa和其他T-box因子诱导斑马鱼左向右组织前体细胞(称为背部前体细胞)的能力，已知这些细胞受到vgll4l的正调控，我们之前已经证明vgll4l基因受到Eomesa的抑制。在这里，我们证明了Eomesa通过连锁的前馈环间接上调vgll4l的表达，这表明在建立左右不对称中发挥了作用。相反，其他T-box因素也不能类似地诱导左右组织者的前身。总体而言，这些发现证明了Eome分子功能的保守性和参与了类似的过程，但由于硬骨鱼中额外的共表达的T-box因子，尽管分子功能明显不同，但在进化过程中要求不同。我们的分析也为Eomesa在斑马鱼左右组织器形成中的作用提供了洞察力。
The T-box family transcription factor Eomesodermin (Eomes) is present in all vertebrates, with many key roles in the developing mammalian embryo and immune system. Homozygous Eomes mutant mouse embryos exhibit early lethality due to defects in both the embryonic mesendoderm and the extraembryonic trophoblast cell lineage. In contrast, zebrafish lacking the predominant Eomes homologue A (Eomesa) do not suffer complete lethality and can be maintained. This suggests fundamental differences in either the molecular function of Eomes orthologues or the molecular configuration of processes in which they participate. To explore these hypotheses we initially analysed the expression of distinct Eomes isoforms in various mouse cell types. Next we compared the functional capabilities of these murine isoforms to zebrafish Eomesa. These experiments provided no evidence for functional divergence. Next we examined the functions of zebrafish Eomesa and other T-box family members expressed in early development, as well as its paralogue Eomesb. Though Eomes is a member of the Tbr1 subfamily we found evidence for functional redundancy with the Tbx6 subfamily member Tbx16, known to be absent from eutherians. However, Tbx16 does not appear to synergise with Eomesa cofactors Mixl1 and Gata5. Finally, we analysed the ability of Eomesa and other T-box factors to induce zebrafish left-right organiser progenitors (known as dorsal forerunner cells) known to be positively regulated by vgll4l, a gene we had previously shown to be repressed by Eomesa. Here we demonstrate that Eomesa indirectly upregulates vgll4l expression via interlocking feedforward loops, suggesting a role in establishment of left-right asymmetry. Conversely, other T-box factors could not similarly induce left-right organiser progenitors. Overall these findings demonstrate conservation of Eomes molecular function and participation in similar processes, but differential requirements across evolution due to additional co-expressed T-box factors in teleosts, albeit with markedly different molecular capabilities. Our analyses also provide insights into the role of Eomesa in left-right organiser formation in zebrafish.
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影响因子：
10.7
作者：
Ahn, Daegwon;You, Kwan-Hee;Kim, Cheol-Hee
通讯作者：
Kim, Cheol-Hee
影响因子：
14.9
作者：
ADAMS, SE;JOHNSON, ID;EDWARDS, RM
通讯作者：
EDWARDS, RM
影响因子：
11.8
作者：
Bjornson, CRR;Griffin, KJR;Kimelman, D
通讯作者：
Kimelman, D
影响因子：
10.5
作者：
Arnold, Sebastian J.;Huang, Guo-Jen;Groszer, Matthias
通讯作者：
Groszer, Matthias
DOI：
10.1242/dev.014357
发表时间：
2008-02
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Arnold SJ;Hofmann UK;Bikoff EK;Robertson EJ
通讯作者：
Robertson EJ