Cooperative Wnt-Nodal Signals Regulate the Patterning of Anterior Neuroectoderm.
Cooperative Wnt-Nodal Signals Regulate the Patterning of Anterior Neuroectoderm.
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DOI：
10.1371/journal.pgen.1006001
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发表时间：
2016-04
期刊：
影响因子：
4.5
通讯作者：
Yaguchi S
中科院分区：
文献类型：
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作者：
Yaguchi J;Takeda N;Inaba K;Yaguchi S
当早期典型Wnt被实验抑制时，海胆胚胎体现了体内默认模型的概念，因为大多数外胚层细胞的命运被指定为前神经外胚层。使用这个模型，我们在这里描述了正交功能的前后Wnt和背腹Nodal信号和它们的靶向转录因子FoxQ 2和Homeobrain的组合如何调节正常神经外胚层的精确模式，其中多巴胺能神经元仅在背侧/侧边缘分化。功能丧失实验表明，腹侧Nodal是通过维持foxQ 2和抑制同源蛋白表达来抑制神经外胚层腹侧中的多巴胺能神经命运所必需的。此外，非典型的Wnt抑制homeobrain在前端的神经外胚层，在神经元能神经元不分化。然而，经典Wnt抑制foxQ 2以促进神经分化。因此，神经外胚层的三维复杂图案是由合作信号产生的，这对于胚胎发生期间初级和次级体轴的形成至关重要。海胆胚胎类似于脊椎动物胚胎，因为默认的细胞命运是潜在的神经源性的，并且正常发育将神经命运限制在位于胚胎前部/背部区域的狭窄区域。由于胚胎需要维持前/背区域的默认神经命运来精确整合来自初级前后和次级背腹体轴的信息，因此这些轴必须通过某些机制相互连接。在这项研究中，我们描述了正交功能的信号通路的组合如何调节其靶向转录因子在前神经外胚层表达，以限制和模式的默认神经原性区域。通过使用海胆胚胎的功能丧失实验，我们揭示了经典和非经典Wnt通路调节沿着主轴的前神经外胚层图案化，并且TGF-β信号控制沿沿着次轴的神经外胚层图案化。此外，我们发现Wnt和TGF-β通路之间的串扰在调节神经外胚层模式中是重要的。由于一些后口类胚胎（包括胚胎干细胞）的默认细胞命运是神经源性的，我们的发现可能是协调沿沿着不同胚胎轴的剩余和/或抑制发育程序的广泛机制，因为Nodal和Wnt信号在许多胚胎中建立早期发育极性中至关重要。
When early canonical Wnt is experimentally inhibited, sea urchin embryos embody the concept of a Default Model in vivo because most of the ectodermal cell fates are specified as anterior neuroectoderm. Using this model, we describe here how the combination of orthogonally functioning anteroposterior Wnt and dorsoventral Nodal signals and their targeting transcription factors, FoxQ2 and Homeobrain, regulates the precise patterning of normal neuroectoderm, of which serotonergic neurons are differentiated only at the dorsal/lateral edge. Loss-of-function experiments revealed that ventral Nodal is required for suppressing the serotonergic neural fate in the ventral side of the neuroectoderm through the maintenance of foxQ2 and the repression of homeobrain expression. In addition, non-canonical Wnt suppressed homeobrain in the anterior end of the neuroectoderm, where serotonergic neurons are not differentiated. Canonical Wnt, however, suppresses foxQ2 to promote neural differentiation. Therefore, the three-dimensionally complex patterning of the neuroectoderm is created by cooperative signals, which are essential for the formation of primary and secondary body axes during embryogenesis. The sea urchin embryo is similar to vertebrate embryos in that the default cell fate is potentially neurogenic, and normal development restricts the neural fate to the narrow area that locates at the anterior/dorsal region of the embryo. Because maintaining the default neural fate to the anterior/dorsal region is required for embryos to precisely integrate information from both the primary anterior-posterior and secondary dorsal-ventral body axes, these axes must be mutually linked by some mechanisms. In this study, we describe how the combination of orthogonally functioning signaling pathways regulates their targeting transcription factors expressing at the anterior neuroectoderm to restrict and pattern the default neurogenic region. By loss-of-function experiments using sea urchin embryos, we revealed that canonical and non-canonical Wnt pathways regulate the anterior neuroectoderm patterning along the primary axis, and TGF-ß signals control the patterning of the neuroectoderm along the secondary axis. In addition, we showed that the crosstalk between the Wnt and TGF-ß pathways was of importance in regulating the neuroectoderm patterning. As the default cell fate in some deuterostome embryos, including embryonic stem cells, is neurogenic, our findings could be widespread mechanisms to coordinate the remaining and/or suppressing developmental programs along different embryonic axes because Nodal and Wnt signals are critical in establishing early developmental polarities in many embryos.