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The emergence of mesencephalic trigeminal neurons.
Neural Development ( IF 3.6 ) Pub Date : 2017-06-24 , DOI: 10.1186/s13064-017-0088-z Marcela Lipovsek 1 , Julia Ledderose 2, 3 , Thomas Butts 1, 4 , Tanguy Lafont 1 , Clemens Kiecker 1 , Andrea Wizenmann 2 , Anthony Graham 1
Neural Development ( IF 3.6 ) Pub Date : 2017-06-24 , DOI: 10.1186/s13064-017-0088-z Marcela Lipovsek 1 , Julia Ledderose 2, 3 , Thomas Butts 1, 4 , Tanguy Lafont 1 , Clemens Kiecker 1 , Andrea Wizenmann 2 , Anthony Graham 1
Affiliation
BACKGROUND
The cells of the mesencephalic trigeminal nucleus (MTN) are the proprioceptive sensory neurons that innervate the jaw closing muscles. These cells differentiate close to the two key signalling centres that influence the dorsal midbrain, the isthmus, which mediates its effects via FGF and WNT signalling and the roof plate, which is a major source of BMP signalling as well as WNT signalling.
METHODS
In this study, we have set out to analyse the importance of FGF, WNT and BMP signalling for the development of the MTN. We have employed pharmacological inhibitors of these pathways in explant cultures as well as utilising the electroporation of inhibitory constructs in vivo in the chick embryo.
RESULTS
We find that interfering with either FGF or WNT signalling has pronounced effects on MTN development whilst abrogation of BMP signalling has no effect. We show that treatment of explants with either FGF or WNT antagonists results in the generation of fewer MTN neurons and affects MTN axon extension and that inhibition of both these pathways has an additive effect. To complement these studies, we have used in vivo electroporation to inhibit BMP, FGF and WNT signalling within dorsal midbrain cells prior to, and during, their differentiation as MTN neurons. Again, we find that inhibition of BMP signalling has no effect on the development of MTN neurons. We additionally find that cells electroporated with inhibitory constructs for either FGF or WNT signalling can differentiate as MTN neurons suggesting that these pathways are not required cell intrinsically for the emergence of these neurons. Indeed, we also show that explants of dorsal mesencephalon lacking both the isthmus and roof plate can generate MTN neurons. However, we did find that inhibiting FGF or WNT signalling had consequences for MTN differentiation.
CONCLUSIONS
Our results suggest that the emergence of MTN neurons is an intrinsic property of the dorsal mesencephalon of gnathostomes, and that this population undergoes expansion, and maturation, along with the rest of the dorsal midbrain under the influence of FGF and WNT signalling.
中文翻译:
中脑三叉神经元的出现。
背景技术中脑三叉神经核(MTN)的细胞是支配下颌闭合肌肉的本体感觉神经元。这些细胞在靠近影响背中脑的两个关键信号中心(峡部)附近分化,地峡通过FGF和WNT信号以及顶板(其是BMP信号以及WNT信号的主要来源)介导其作用。方法在本研究中,我们着手分析FGF,WNT和BMP信号对于MTN发育的重要性。我们已经在外植体培养物中以及在鸡胚体内利用抑制性构建体的电穿孔方法采用了这些途径的药理抑制剂。结果我们发现干扰FGF或WNT信号传导对MTN发育有明显影响,而BMP信号传导的废除则没有影响。我们表明,用FGF或WNT拮抗剂处理外植体会导致产生更少的MTN神经元并影响MTN轴突的延伸,并且抑制这两种途径都具有累加作用。为了补充这些研究,我们在分化为MTN神经元之前和过程中使用了体内电穿孔来抑制背中脑细胞内的BMP,FGF和WNT信号传导。同样,我们发现抑制BMP信号传导对MTN神经元的发育没有影响。我们还发现,用FGF或WNT信号抑制性构建物电穿孔的细胞可以分化为MTN神经元,表明这些神经元的出现并不是细胞固有的这些途径。确实,我们还表明,缺乏峡部和顶板的背中脑外植体可产生MTN神经元。但是,我们确实发现抑制FGF或WNT信号传导对MTN分化具有影响。结论我们的研究结果表明,MTN神经元的出现是造嘴背侧中脑的内在特性,在FGF和WNT信号的影响下,该群体与背中脑的其余部分一起经历了扩张和成熟。我们还显示,缺乏峡部和顶板的背中脑外植体可产生MTN神经元。但是,我们确实发现抑制FGF或WNT信号传导对MTN分化具有影响。结论我们的研究结果表明,MTN神经元的出现是造嘴背侧中脑的内在特性,在FGF和WNT信号的影响下,该群体与背中脑的其余部分一起经历了扩张和成熟。我们还显示,缺乏峡部和顶板的背中脑外植体可产生MTN神经元。但是,我们确实发现抑制FGF或WNT信号传导对MTN分化具有影响。结论我们的研究结果表明,MTN神经元的出现是造嘴背侧中脑的内在特性,在FGF和WNT信号的影响下,该群体与背中脑的其余部分一起经历了扩张和成熟。
更新日期:2019-11-01
中文翻译:
中脑三叉神经元的出现。
背景技术中脑三叉神经核(MTN)的细胞是支配下颌闭合肌肉的本体感觉神经元。这些细胞在靠近影响背中脑的两个关键信号中心(峡部)附近分化,地峡通过FGF和WNT信号以及顶板(其是BMP信号以及WNT信号的主要来源)介导其作用。方法在本研究中,我们着手分析FGF,WNT和BMP信号对于MTN发育的重要性。我们已经在外植体培养物中以及在鸡胚体内利用抑制性构建体的电穿孔方法采用了这些途径的药理抑制剂。结果我们发现干扰FGF或WNT信号传导对MTN发育有明显影响,而BMP信号传导的废除则没有影响。我们表明,用FGF或WNT拮抗剂处理外植体会导致产生更少的MTN神经元并影响MTN轴突的延伸,并且抑制这两种途径都具有累加作用。为了补充这些研究,我们在分化为MTN神经元之前和过程中使用了体内电穿孔来抑制背中脑细胞内的BMP,FGF和WNT信号传导。同样,我们发现抑制BMP信号传导对MTN神经元的发育没有影响。我们还发现,用FGF或WNT信号抑制性构建物电穿孔的细胞可以分化为MTN神经元,表明这些神经元的出现并不是细胞固有的这些途径。确实,我们还表明,缺乏峡部和顶板的背中脑外植体可产生MTN神经元。但是,我们确实发现抑制FGF或WNT信号传导对MTN分化具有影响。结论我们的研究结果表明,MTN神经元的出现是造嘴背侧中脑的内在特性,在FGF和WNT信号的影响下,该群体与背中脑的其余部分一起经历了扩张和成熟。我们还显示,缺乏峡部和顶板的背中脑外植体可产生MTN神经元。但是,我们确实发现抑制FGF或WNT信号传导对MTN分化具有影响。结论我们的研究结果表明,MTN神经元的出现是造嘴背侧中脑的内在特性,在FGF和WNT信号的影响下,该群体与背中脑的其余部分一起经历了扩张和成熟。我们还显示,缺乏峡部和顶板的背中脑外植体可产生MTN神经元。但是,我们确实发现抑制FGF或WNT信号传导对MTN分化具有影响。结论我们的研究结果表明,MTN神经元的出现是造嘴背侧中脑的内在特性,在FGF和WNT信号的影响下,该群体与背中脑的其余部分一起经历了扩张和成熟。