Regulation of canonical Wnt signaling by Brachyury is essential for posterior mesoderm formation.

Regulation of canonical Wnt signaling by Brachyury is essential for posterior mesoderm formation.
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DOI:
10.1016/j.devcel.2008.04.013
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发表时间:
2008-07
期刊:
影响因子:
11.8
通讯作者:
Kimelman, David
Kimelman, David
中科院分区:
生物学1区
文献类型:
--
作者:
Martin, Benjamin L.;Kimelman, David

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T 盒转录因子 Brachyury 对于所有脊椎动物后体的形成至关重要,尽管其关键转录靶标仍然难以捉摸。对小鼠 Brachyury 和斑马鱼 Brachyury 直系同源物 Ntl 的功能丧失研究表明,Brachyury 在高等脊椎动物中比在低等脊椎动物中发挥更重要的作用。我们已经鉴定了第二个斑马鱼 Brachyury 直系同源物 (Bra),并表明 Ntl 和 Bra 的联合丢失重现了小鼠表型,证明了 Brachyury 在除最前体节之外的所有体节模式中发挥着古老的作用。通过细胞移植,我们证明 Brachury 在体节形成过程中唯一重要的作用是非细胞自主的,并证明 Ntl 和 Bra 是经典 Wnts wnt8 和 wnt3a 的表达所必需的,并且可以诱导其表达。我们提出,Ntl/Bra 和经典 Wnt 信号之间的正向自动调节环路可维持中胚层祖细胞,以促进脊索动物后体节的发育。
The T-box transcription factor Brachyury is essential for the formation of the posterior body in all vertebrates, although its critical transcriptional targets have remained elusive. Loss of function studies of mouse Brachyury and the zebrafish Brachyury ortholog Ntl indicated that Brachury plays a more significant role in higher vertebrates than lower vertebrates. We have identified a second zebrafish Brachyury ortholog (Bra), and show that a combined loss of Ntl and Bra recapitulates the mouse phenotype, demonstrating an ancient role for Brachyury in patterning all but the most anterior somites. Using cell transplantation we show that the only essential role for Brachury during somite formation is non cell-autonomous, and demonstrate that Ntl and Bra are required for and can induce expression of the canonical Wnts wnt8 and wnt3a. We propose that a positive autoregulatory loop between Ntl/Bra and canonical Wnt signaling maintains the mesodermal progenitors to facilitate posterior somite development in chordates.
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