Lack of Fgf18 causes abnormal clustering of motor nerve terminals at the neuromuscular junction with reduced acetylcholine receptor clusters.
Lack of Fgf18 causes abnormal clustering of motor nerve terminals at the neuromuscular junction with reduced acetylcholine receptor clusters.
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DOI：
10.1038/s41598-017-18753-5
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发表时间：
2018-01-11
影响因子：
4.6
通讯作者：
Ohno K
中科院分区：
文献类型：
--
作者：
Ito K;Ohkawara B;Yagi H;Nakashima H;Tsushima M;Ota K;Konishi H;Masuda A;Imagama S;Kiyama H;Ishiguro N;Ohno K
FGF受体2参与神经肌肉接头（NMJ）的形成，但其体内配体仍有待确定。对小鼠脊髓运动神经元 (SMN) 的激光捕获显微解剖显示，Fgf18 mRNA 在成人 SMN 中高度表达。 Fgf18 mRNA在胚胎第15.5天在脊髓中表达最高，到出生后第7天逐渐下降。在E18.5和成人中，FGF18蛋白定位于胫骨前肌的NMJ。 E18.5 的 Fgf18−/− 小鼠膈肌中 NMJ 特异性 Chrne 和 Colq 基因的表达减少。在Fgf18−/−膈肌中，神经末梢的突触素阳性区域和运动终板的乙酰胆碱受体（AChR）阳性区域均约为野生型胚胎中的三分之一。 Fgf18-/-隔膜超微结构显示多个神经末梢的异常聚集，形成巨大的突触前，具有稀疏的突触囊泡和简化的运动终板。在 Fgf18−/− 隔膜中，微型终板电位振幅较低，频率显着降低。在 C2C12 肌管中，FGF18 增强了 AChR 聚类，而抑制 FGFR 或 MEK1 可以阻断这种作用。我们认为 FGF18 在小鼠胚胎发生中的 AChR 聚类和 NMJ 形成中发挥关键作用。
FGF receptor 2 is involved in the formation of the neuromuscular junction (NMJ), but its in vivo ligand remains to be determined. Laser capture microdissection of the mouse spinal motor neurons (SMNs) revealed that Fgf18 mRNA is highly expressed in SMNs in adults. Expression of Fgf18 mRNA was the highest in the spinal cord at embryonic day (E) 15.5, which gradually decreased to postnatal day 7. FGF18 protein was localized at the NMJs of the tibialis anterior muscle at E18.5 and in adults. Fgf18−/− mice at E18.5 showed decreased expressions of the NMJ-specific Chrne and Colq genes in the diaphragm. In Fgf18−/− diaphragms, the synaptophysin-positive areas at the nerve terminals and the acetylcholine receptor (AChR)-positive areas at the motor endplates were both approximately one-third of those in wild-type embryos. Fgf18−/− diaphragms ultrastructurally showed abnormal aggregation of multiple nerve terminals making a gigantic presynapse with sparse synaptic vesicles, and simplified motor endplates. In Fgf18−/− diaphragms, miniature endplate potentials were low in amplitude with markedly reduced frequency. In C2C12 myotubes, FGF18 enhanced AChR clustering, which was blocked by inhibiting FGFRs or MEK1. We propose that FGF18 plays a pivotal role in AChR clustering and NMJ formation in mouse embryogenesis.
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影响因子：
4.6
作者：
Nakashima H;Ohkawara B;Ishigaki S;Fukudome T;Ito K;Tsushima M;Konishi H;Okuno T;Yoshimura T;Ito M;Masuda A;Sobue G;Kiyama H;Ishiguro N;Ohno K
通讯作者：
Ohno K
影响因子：
10.5
作者：
Brewer JR;Mazot P;Soriano P
通讯作者：
Soriano P
影响因子：
3.4
作者：
ENGEL, AG;NAGEL, A;WAISBURG, HA
通讯作者：
WAISBURG, HA
影响因子：
2.6
作者：
Ohuchi, H;Kimura, S;Itoh, N
通讯作者：
Itoh, N
影响因子：
10.5
作者：
Liu, ZH;Xu, JS;Ornitz, DM
通讯作者：
Ornitz, DM