Institute for Amphibian Biology, Hiroshima University Graduate School of Science, Kagamiyama 1-3-1, Higashi-Hiroshima, Japan.
Dev Biol. 2011 Dec 1;360(1):11-29. doi: 10.1016/j.ydbio.2011.09.005. Epub 2011 Sep 16.
The formation of the dorsal-ventral (DV) and anterior-posterior (AP) axes, fundamental to the body plan of animals, is regulated by several groups of polypeptide growth factors including the TGF-β, FGF, and Wnt families. In order to ensure the establishment of the body plan, the processes of DV and AP axis formation must be linked and coordinately regulated. However, the molecular mechanisms responsible for these interactions remain unclear. Here, we demonstrate that the forkhead box transcription factor FoxB1, which is upregulated by the neuralizing factor Oct-25, plays an important role in the formation of the DV and AP axes. Overexpression of FoxB1 promoted neural induction and inhibited BMP-dependent epidermal differentiation in ectodermal explants, thereby regulating the DV patterning of the ectoderm. In addition, FoxB1 was also found to promote the formation of posterior neural tissue in both ectodermal explants and whole embryos, suggesting its involvement in embryonic AP patterning. Using knockdown analysis, we found that FoxB1 is required for the formation of posterior neural tissues, acting in concert with the Wnt and FGF pathways. Consistent with this, FoxB1 suppressed the formation of anterior structures via a process requiring the function of XWnt-8 and eFGF. Interestingly, while downregulation of FoxB1 had little effect on neural induction, we found that it functionally interacted with its upstream factor Oct-25 and plays a supportive role in the induction and/or maintenance of neural tissue. Our results suggest that FoxB1 is part of a mechanism that fine-tunes, and leads to the coordinated formation of, the DV and AP axes during early development.
背腹(DV)和前后(AP)轴的形成是动物体计划的基础,受包括 TGF-β、FGF 和 Wnt 家族在内的几组多肽生长因子的调节。为了确保体计划的建立,DV 和 AP 轴形成的过程必须联系起来并协调调节。然而,负责这些相互作用的分子机制尚不清楚。在这里,我们证明叉头框转录因子 FoxB1 在上调神经因子 Oct-25 的过程中发挥重要作用,在 DV 和 AP 轴的形成中发挥重要作用。FoxB1 的过表达促进了神经诱导,抑制了外胚层外植体中 BMP 依赖性表皮分化,从而调节了外胚层的 DV 模式。此外,还发现 FoxB1 还促进了外胚层外植体和整个胚胎中后部神经组织的形成,表明其参与了胚胎 AP 模式的形成。通过敲低分析,我们发现 FoxB1 是后部神经组织形成所必需的,与 Wnt 和 FGF 途径协同作用。与此一致,FoxB1 通过需要 XWnt-8 和 eFGF 功能的过程抑制前部结构的形成。有趣的是,虽然 FoxB1 的下调对神经诱导几乎没有影响,但我们发现它与其上游因子 Oct-25 相互作用,并在神经组织的诱导和/或维持中发挥支持作用。我们的研究结果表明,FoxB1 是一个精细调节并导致早期发育中 DV 和 AP 轴协调形成的机制的一部分。