Bmp and Wnt/beta-catenin signals control expression of the transcription factor Olig3 and the specification of spinal cord neurons.
Bmp and Wnt/beta-catenin signals control expression of the transcription factor Olig3 and the specification of spinal cord neurons.
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DOI：
10.1016/j.ydbio.2006.10.045
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发表时间：
2007-03
影响因子：
2.7
通讯作者：
D. Zechner;T. Müller;H. Wende;Ingrid Walther;M. Taketo;E. Bryan Crenshaw;M. Treier;W. Birchmeier;C. Birchmeier
中科院分区：
文献类型：
--
作者：
D. Zechner;T. Müller;H. Wende;Ingrid Walther;M. Taketo;E. Bryan Crenshaw;M. Treier;W. Birchmeier;C. Birchmeier
在发育中的脊髓中，顶板的信号决定了背祖结构域，并控制了三种神经元类型的规范，即背中间神经元dI1、dI2和dI3。Bmp和Wnt/β-catenin信号以及转录因子如Olig3或Ngn1/2在这一过程中至关重要。我们研究了Bmp和Wnt/β-catenin信号与转录因子Olig3在脊髓背侧模式中的上位性关系。利用小鼠β-catenin功能获得和复合β-catenin功能获得/Olig3功能丧失突变，我们可以发现Wnt/β-catenin信号在dI2和dI3神经元的调控中作用于Olig3的上游。对这种复合突变小鼠的分析使我们能够区分Wnt/β-catenin信号在背祖细胞增殖和模式化中的两种功能。通过鸡脊髓电穿孔实验，我们进一步证明Bmp信号在Wnt/β-catenin的上游调控Olig3，并且Wnt/β-catenin信号在调控Olig3表达中起指导作用。我们得出结论，Wnt/β-catenin和BMP信号协调控制脊髓背神经元的规范。
In the developing spinal cord, signals of the roof plate pattern the dorsal progenitor domain and control the specification of three neuron types, dorsal interneurons dI1, dI2, and dI3. Bmp and Wnt/β-catenin signals as well as transcription factors like Olig3 or Ngn1/2 are essential in this process. We have studied the epistatic relationship between Bmp and Wnt/β-catenin signals and the transcription factor Olig3 in dorsal spinal cord patterning. Using β-catenin gain-of-function and compound β-catenin gain-of-function/Olig3 loss-of-function mutations in mice, we could show that Wnt/β-catenin signals act upstream of Olig3 in the specification of dI2 and dI3 neurons. The analysis of such compound mutant mice allowed us to distinguish between the two functions of Wnt/β-catenin signaling in proliferation and patterning of dorsal progenitors. Using electroporation of chick spinal cords, we further demonstrate that Bmp signals act upstream of Wnt/β-catenin in the regulation of Olig3 and that Wnt/β-catenin signals play an instructive role in controlling Olig3 expression. We conclude that Wnt/β-catenin and BMP signals coordinately control the specification of dorsal neurons in the spinal cord.