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首页> 外文期刊>Cell and Tissue Research >Differentiation of autonomic neurons by BMP-independent mechanisms.
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Differentiation of autonomic neurons by BMP-independent mechanisms.

机译:通过独立于BMP的机制分化自主神经元。

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摘要

A number of signaling molecules and transcription factors play important roles in the development of the autonomic nervous system. Here, we show that mouse trunk neural crest cells can differentiate into autonomic neurons expressing mammalian achaete-scute homolog 1 (mash1), Phox2b, tyrosine hydroxylase, and/or dopamine-beta-hydroxylase in the absence of bone morphogenetic protein (BMP)-4. The expression of mash1 and Phox2b is induced even in the presence of noggin or chordin, which are inhibitors of BMP signaling. Whereas these autonomic neurons do not express c-ret, the receptor for glial-cell-line-derived neurotrophic factor (GDNF), GDNF promotes the differentiation of c-ret-positive autonomic neurons in the presence of noggin. Autonomic neurogenesis is completely prevented by fibroblast growth factor (FGF)-2 treatment or by activation of Notch signaling. Furthermore, the suppression of Phox2b expression by FGF-2 can be recovered by treatment with Notch-1 small interfering RNA. Our data suggest thatBMP-independent mechanisms promote the differentiation of autonomic neurons, and that FGF-2 suppresses autonomic neurogenesis by means of the activation of Notch signaling.
机译:许多信号分子和转录因子在植物神经系统的发育中起重要作用。在这里,我们表明,在没有骨形态发生蛋白(BMP)的情况下,小鼠躯干神经c细胞可以分化为表达哺乳动物achaete-scute同源物1(mash1),Phox2b,酪氨酸羟化酶和/或多巴胺-β-羟化酶的自主神经元。 4。 mash1和Phox2b的表达甚至在存在Noggin或chordin(它们是BMP信号转导的抑制剂)的情况下也被诱导。这些自主神经元不表达神经胶质细胞系神经营养因子(GDNF)的受体c-ret,而在头蛋白存在的情况下,GDNF促进c-ret阳性自主神经元的分化。自主神经发生被成纤维细胞生长因子(FGF)-2治疗或Notch信号激活完全阻止。此外,通过用Notch-1小干扰RNA处理,可以恢复FGF-2对Phox2b表达的抑制。我们的数据表明独立于BMP的机制促进了自主神经元的分化,而FGF-2通过激活Notch信号抑制了自主神经的发生。

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