Celsr3 Inactivation in the Brainstem Impairs Rubrospinal Tract Development and Mouse Behaviors in Motor Coordination and Mechanic-Induced Response.
Celsr3 Inactivation in the Brainstem Impairs Rubrospinal Tract Development and Mouse Behaviors in Motor Coordination and Mechanic-Induced Response.
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DOI：
10.1007/s12035-022-02910-7
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发表时间：
2022-08
影响因子：
5.1
通讯作者：
Zhou, Libing
中科院分区：
文献类型：
--
作者：
Chen, Boli;Li, Fuxiang;Jia, Bin;So, Kwok-Fai;Wei, Ji-An;Liu, Yuchu;Qu, Yibo;Zhou, Libing
前脑中Celsr3的失活导致纵向轴突束如皮质脊髓束的缺陷。在这项研究中，我们使用En1-Cre小鼠（Celsr3 cKO）灭活了脑干中的Celsr3，并分析了轴突和行为表型。Celsr3 cKO动物显示脊髓节段的红脊髓轴突减少83%，皮质脊髓轴突减少30%，与腹角多巴胺能纤维分支增加有关。在突变动物中，脊髓运动神经元、神经肌肉连接和二头肌肌电信号振幅也减少。突变小鼠的运动协调能力受损，对重型机械刺激的反应有缺陷，但在行走和处理食物颗粒方面没有残疾。经突触示踪表明，在背角深层脊髓神经元上存在红脊髓轴突突触，后肢的机械刺激在对照小鼠中诱导了强的红核钙信号，而突变小鼠中不太明显。综上所述，Celsr3以细胞和非细胞自主的方式调节脊髓下行轴突和运动网络的发育，而红脊髓系统的成熟是运动协调和对机械刺激的反应所必需的。在线版本包含补充材料，可在10.1007/s12035-022-02910-7获得。
Inactivation of Celsr3 in the forebrain results in defects of longitudinal axonal tracts such as the corticospinal tract. In this study, we inactivated Celsr3 in the brainstem using En1-Cre mice (Celsr3 cKO) and analyzed axonal and behavioral phenotypes. Celsr3 cKO animals showed an 83% reduction of rubrospinal axons and 30% decrease of corticospinal axons in spinal segments, associated with increased branching of dopaminergic fibers in the ventral horn. Decreases of spinal motoneurons, neuromuscular junctions, and electromyographic signal amplitude of the biceps were also found in mutant animals. Mutant mice had impaired motor coordination and defective response to heavy mechanical stimulation, but no disability in walking and food pellet handling. Transsynaptic tracing demonstrated that rubrospinal axons synapse on spinal neurons in the deep layer of the dorsal horn, and mechanical stimulation of hindpaws induced strong calcium signal of red nuclei in control mice, which was less prominent in mutant mice. In conclusion, Celsr3 regulates development of spinal descending axons and the motor network in cell and non-cell autonomous manners, and the maturation of the rubrospinal system is required for motor coordination and response to mechanical stimulation. The online version contains supplementary material available at 10.1007/s12035-022-02910-7.
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DOI：
10.1523/jneurosci.4508-10.2010
发表时间：
2010-11-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fenstermaker AG;Prasad AA;Bechara A;Adolfs Y;Tissir F;Goffinet A;Zou Y;Pasterkamp RJ
通讯作者：
Pasterkamp RJ
DOI：
10.1093/cercor/bhw132
发表时间：
2016-07
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
--
作者：
Feng J;Xian Q;Guan T;Hu J;Wang M;Huang Y;So KF;Evans SM;Chai G;Goffinet AM;Qu Y;Zhou L
通讯作者：
Zhou L
影响因子：
7.7
作者：
Moreno-Lopez Y;Bichara C;Delbecq G;Isope P;Cordero-Erausquin M
通讯作者：
Cordero-Erausquin M
影响因子：
10.5
作者：
DAVIS, CA;JOYNER, AL
通讯作者：
JOYNER, AL
影响因子：
2.5
作者：
Küchler, M;Fouad, K;Raineteau, O
通讯作者：
Raineteau, O