Department of Cell Biology, University of Alabama, Birmingham, Alabama, USA.
Dev Dyn. 2012 Aug;241(8):1260-73. doi: 10.1002/dvdy.23811. Epub 2012 Jun 15.
Smad ubiquitination regulatory factor (Smurf) 1 and 2 are E3 ubiquitin ligases originally identified as inhibitors of transforming growth factor beta signaling and are shown to modulate multiple cellular activities. The roles of Smurfs in vertebrate embryogenesis, however, are not completely understood.
Here we investigate the function of Smurf2 during early Xenopus development. We show that distinctly from Smurf1, overexpression of Smurf2 in presumptive mesoderm interfered with mesoderm induction and caused axial defects, whereas knockdown of Smurf2 with antisense morpholino oligonucleotides resulted in expansion of the mesoderm. These results imply that Smurf2 may modulate nodal-mediated mesodermal induction. Consistently, ventral expression of Smurf2 induced a partial secondary axis with head structures. In the ectoderm, Smurf2 resembled Smurf1 in controlling neural and epidermal marker expression and influencing head formation. Smurf1, but not Smurf2, additionally affected neural tube closure. Interestingly, both Smurfs could enhance as well as repress neural crest markers, implying that they modulate their targets dynamically during neural plate border specification.
Our data demonstrate that Smurf1 and Smurf2 have overlapping and distinct functionalities during early frog embryogenesis; collectively, they regulate ectodermal and mesodermal induction and patterning to ensure normal development of Xenopus embryos.
Smad 泛素化调节因子（Smurf）1 和 2 最初被鉴定为转化生长因子β信号的抑制剂，是 E3 泛素连接酶，被证明可以调节多种细胞活动。然而，Smurfs 在脊椎动物胚胎发生中的作用尚未完全了解。
在这里，我们研究了 Smurf2 在早期非洲爪蟾发育过程中的功能。与 Smurf1 不同，我们发现 Smurf2 在假定的中胚层中的过表达干扰了中胚层诱导，并导致了轴突缺陷，而反义寡核苷酸介导的 Smurf2 敲低导致中胚层的扩张。这些结果表明 Smurf2 可能调节 nodal 介导的中胚层诱导。一致地，Smurf2 的腹侧表达诱导了具有头部结构的部分次级轴。在外胚层中，Smurf2 类似于 Smurf1 控制神经和表皮标记物的表达并影响头部形成。Smurf1 但不是 Smurf2 还影响神经管闭合。有趣的是，Smurfs 都可以增强和抑制神经嵴标记物，这表明它们在神经板边界特化期间动态地调节其靶标。
我们的数据表明 Smurf1 和 Smurf2 在早期非洲爪蟾胚胎发生中具有重叠和独特的功能；它们共同调节外胚层和中胚层的诱导和模式形成，以确保非洲爪蟾胚胎的正常发育。
