Eafs control erythroid cell fate by regulating c-myb expression through Wnt signaling.
Eafs control erythroid cell fate by regulating c-myb expression through Wnt signaling.
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DOI：
10.1371/journal.pone.0064576
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu JX
中科院分区：
文献类型：
--
作者：
Ma X;Liu JX
ELL相关因子1和ELL相关因子2（EAF 1/2 factors）在肿瘤抑制和胚胎发育中起重要作用。我们以前的研究表明，eaf因子介导有效的收敛和延伸（C&E）的运动和调制中胚层和神经模式，通过调节非经典和经典的Wnt信号在早期胚胎过程。在本研究中，通过敲低胚胎中eaf 1和eaf 2，我们发现原代红系细胞的分化被阻断，但造血前体细胞在eaf突变体中得以维持。共同注射c-myb-MO挽救了eafs morphants中的红系分化，如红系特异性基因βe3珠蛋白的恢复表达所示。此外，低剂量c-myb可有效阻断胚胎中βe3珠蛋白的表达，而不影响造血祖细胞和其他中胚层标志物的表达，这与我们在eafs变形体中观察到的表型相似。我们还发现，通过在芽期胚胎中瞬时诱导dn-Tcf来敲低Wnt信号转导，将增加的c-myb下调至正常水平，并且还恢复了eafs morphants中βe3珠蛋白的表达。我们的证据表明，eaf因子在通过经典Wnt信号调节c-Myb表达来控制红系细胞命运中具有新的作用。
ELL associated factor 1 and ELL associated factor 2 (EAF1/2 factors) are reported to play important roles in tumor suppression and embryogenesis. Our previous studies showed that eaf factors mediated effective convergence and extension (C&E) movements and modulated mesoderm and neural patterning by regulating both non-canonical and canonical Wnt signaling in the early embryonic process. In this study, through knockdown of both eaf1 and eaf2 in embryos, we found that differentiation of primary erythroid cells was blocked, but hematopoietic precursor cells maintained in eafs morphants. Co-injection of c-myb-MO rescued the erythroid differentiation in eafs morphants, as indicated by the restored expression of the erythroid-specific gene, βe3 globin. In addition, low dosage of c-myb effectively blocked the βe3 globin expression in embryos, and did not affect the expression of markers of hematopoietic progenitor cells and other mesoderm, which was similar to the phenotypes we observed in eafs morphants. We also revealed that knockdown Wnt signaling by transiently inducing dn-Tcf in embryos at the bud stage down-regulated the increased c-myb to normal level and also restored βe3 globin expression in eafs morphants. Our evidence points to a novel role for eaf factors in controlling erythroid cell fate by regulating c-Myb expression through canonic Wnt signaling.
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影响因子：
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