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Strong sonic hedgehog signaling in the mouse ventral spinal cord is not required for oligodendrocyte precursor cell (OPC) generation but is necessary for correct timing of its generation
Neurochemistry international ( IF 4.4 ) Pub Date : 2017-11-06 , DOI: 10.1016/j.neuint.2017.11.003
Hirokazu Hashimoto , Wen Jiang , Takeshi Yoshimura , Kyeong-Hye Moon , Jinwoong Bok , Kazuhiro Ikenaka

In the mouse neural tube, sonic hedgehog (Shh) secreted from the floor plate (FP) and the notochord (NC) regulates ventral patterning of the neural tube, and later is essential for the generation of oligodendrocyte precursor cells (OPCs). During early development, the NC is adjacent to the neural tube and induces ventral domains in it, including the FP. In the later stage of development, during gliogenesis in the spinal cord, the pMN domain receives strong Shh signaling input. While this is considered to be essential for the generation of OPCs, the actual role of this strong input in OPC generation remains unclear. Here we studied OPC generation in bromi mutant mice which show abnormal ciliary structure. Shh signaling occurs within cilia and has been reported to be weak in bromi mutants. At E11.5, accumulation of Patched1 mRNA, a Shh signaling reporter, is observed in the pMN domain of wild type but not bromi mutants, whereas expression of Gli1 mRNA, another Shh reporter, disappeared. Thus, Shh signaling input to the pMN domain at E12.5 was reduced in bromi mutant mice. In these mutants, induction of the FP structure was delayed and its size was reduced compared to wild type mice. Furthermore, while the p3 and pMN domains were induced, the length of the Nkx2.2-positive region and the number of Olig2-positive cells decreased. The number of OPCs was also significantly decreased in the E12.5 and E14.5 bromi mutant spinal cord. In contrast, motor neuron (MN) production, detected by HB9 expression, significantly increased. It is likely that the transition from MN production to OPC generation in the pMN domain is impaired in bromi mutant mice. These results suggest that strong Shh input to the pMN domain is not required for OPC generation but is essential for producing a sufficient number of OPCs.



中文翻译:

少突胶质细胞前体细胞(OPC)生成并不需要小鼠腹侧脊髓中的强声刺猬信号,但对于正确生成它的时机是必需的

在小鼠神经管中,从底板(FP)和脊索(NC)分泌的声波刺猬(Shh)调节神经管的腹腔模式,后来对于少突胶质细胞前体细胞(OPC)的产生至关重要。在早期发育中,NC与神经管相邻,并在其中诱导腹侧结构域,包括FP。在发育的后期,在脊髓神经胶质发生期间,pMN结构域接受强Shh信号输入。尽管这对于OPC的生成至关重要,但尚不清楚在OPC生成中这种强大投入的实际作用。在这里,我们研究了显示异常睫状结构的bromi突变小鼠中OPC的产生。Shh信号在纤毛内发生,据报道在溴代微弱突变体。在E11.5处,在野生型的pMN域中观察到Shh信号转导蛋白Patched1 mRNA的积累,但在bromi突变体中未观察到,而另一种Shh报道蛋白Gli1 mRNA的表达却消失了。因此,在bromi突变小鼠中,在E12.5处输入到pMN结构域的Shh信号输入减少了。在这些突变体中,与野生型小鼠相比,FP结构的诱导被延迟并且其大小减小。此外,虽然诱导了p3和pMN域,但Nkx2.2阳性区域的长度和Olig2阳性细胞的数量减少了。E12.5和E14.5溴中的OPC数量也显着减少突变型脊髓。相反,通过HB9表达检测到的运动神经元(MN)产生显着增加。在bromi突变小鼠中,pMN域中从MN生成到OPC生成的过渡很可能受到了损害。这些结果表明,向OMN生成不需要向pMN域强输入Shh,但对于产生足够数量的OPC则是必不可少的。

更新日期:2017-11-06
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