Notch signaling is required for the chondrogenic specification of mouse mesencephalic neural crest cells
Notch signaling is required for the chondrogenic specification of mouse mesencephalic neural crest cells
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DOI：
10.1016/j.mod.2006.12.002
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发表时间：
2007-03-01
影响因子：
2.6
通讯作者：
Ito, Kazuo
中科院分区：
文献类型：
--
作者：
Nakanishi, Kouichi;Chan, Yuet Sim;Ito, Kazuo
我们研究了Notch信号在小鼠中脑神经嵴细胞软骨形成中的作用。本研究表明，Notch信号的激活或成纤维细胞生长因子（FGFs）的治疗可促进表达11型胶原的增殖性和前增生性软骨细胞的分化。Notch激活或FGF2暴露在培养的前24天对于增殖和预肥大软骨细胞的分化至关重要。11型胶原的转录激活因子SOX9的表达也通过Notch激活或FGF2处理而上调。通过Notch-1 siRNA抑制Notch信号传导，FGF2促进增殖和前增生性软骨细胞分化的作用被显著抑制。这些结果表明，FGFs激活Notch信号，这种激活促进小鼠中脑神经嵴细胞的软骨形成。此外，我们研究了Notch-1、SOX9和p75（未分化神经嵴细胞的标记物）在中脑神经嵴细胞定植并发生软骨形成的下颌骨弓中的表达模式。这些体内观察，加上目前的体外研究结果，表明Notch信号和FGFs是促进小鼠中脑神经嵴细胞成软骨特异性的上皮间充质相互作用的一个组成部分。2006爱思唯尔爱尔兰有限公司版权所有。
We examined the roles of Notch signaling in the chondrogenesis of mouse mesencephalic neural crest cells. The present study demonstrated that the activation of Notch signaling or the treatment with fibroblast growth factors (FGFs) promotes the differentiation of proliferative and prehypertrophic chondrocytes expressing collagen type 11. Notch activation or FGF2 exposure during the first 24 It in culture was critical for the differentiation of proliferative and prehypertrophic chondrocytes. The expression of SOX9, a transcription activator of collagen type 11, was also upregulated by Notch activation or FGF2 treatment. The promotion of proliferative and prehypertrophic chondrocyte differentiation by FGF2 was significantly suppressed by the inhibition of Notch signaling using Notch-1 siRNA. These results suggest that FGFs activate Notch signaling and that this activation promotes the chondrogenic specification of mouse mesencephalic neural crest cells. Furthermore, we investigated the expression patterns of Notch-1, SOX9, and p75, which is a marker of undifferentiated neural crest cells, in the mandibular arch where mesencephalic neural crest cells colonize and undergo chondrogenesis. These in vivo observations, coupled with the results of the present in vitro study, suggest that Notch signaling as well as FGFs is a component of epithelial mesenchymal interactions that promote the chondrogenic specification of mouse mesencephalic neural crest cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.