College of Fisheries, Huazhong Agricultural University, Wuhan, P. R. China.
PLoS One. 2013 May 22;8(5):e64576. doi: 10.1371/journal.pone.0064576. Print 2013.
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.
ELL 相关因子 1 和 ELL 相关因子 2（EAF1/2 因子）被报道在肿瘤抑制和胚胎发生中发挥重要作用。我们之前的研究表明，eaf 因子通过调节非经典和经典 Wnt 信号通路在早期胚胎发育过程中调节细胞的有效趋同延伸运动（C&E），并调节中胚层和神经模式。在这项研究中，通过在胚胎中敲低 eaf1 和 eaf2，我们发现初级红细胞的分化被阻断，但造血前体细胞在 eafs 突变体中得以维持。c-myb-MO 的共注射挽救了 eafs 突变体中的红细胞分化，如红细胞特异性基因βe3 球蛋白的表达恢复所示。此外，低剂量的 c-myb 有效地阻断了胚胎中βe3 球蛋白的表达，并且不影响造血祖细胞和其他中胚层的标志物的表达，这与我们在 eafs 突变体中观察到的表型相似。我们还揭示了在芽期通过瞬时诱导 dn-Tcf 敲低 Wnt 信号会将增加的 c-myb 下调至正常水平，并在 eafs 突变体中恢复βe3 球蛋白的表达。我们的证据表明，eaf 因子通过经典 Wnt 信号通路调节 c-Myb 表达来控制红细胞命运的新作用。
