Wu X, Howard M J
Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo, Ohio 43614, USA.
Mol Cell Neurosci. 2001 Oct;18(4):394-406. doi: 10.1006/mcne.2001.1032.
Molecules derived from the neural tube and found in chick embryo extract (CEE) and bone morphogenetic proteins (BMP) support the differentiation of neural crest-derived catecholaminergic (CA) neurons. We now report that intracellular signaling resulting in the activation of Map kinase (MapK) or translocation of Smad1 mediate the differentiation of CA neurons in response to CEE or BMP 4, respectively. The differentiation of CA neurons was significantly reduced by inhibiting MapK using PD98059 or by pan-specific blockade of tyrosine kinases using Herbimycin A. In the presence of BMP 4 and inhibitors of MapK signaling, differentiation of CA neurons was only moderately reduced. Independent of MapK, BMP 4 induced translocation of Smad1 from the cytosol to the nucleus and induced transcription of dHAND, a DNA binding protein required for the differentiation of CA neurons. The data suggest that CEE-derived factors and BMP4 support the differentiation of CA neurons via independent signaling pathways.
源自神经管且存在于鸡胚提取物（CEE）和骨形态发生蛋白（BMP）中的分子，能够支持神经嵴衍生的儿茶酚胺能（CA）神经元的分化。我们现在报告，分别导致丝裂原活化蛋白激酶（MapK）激活或Smad1易位的细胞内信号传导，介导了CA神经元对CEE或BMP 4的反应性分化。使用PD98059抑制MapK或使用赫曲霉素A泛特异性阻断酪氨酸激酶，可显著降低CA神经元的分化。在存在BMP 4和MapK信号传导抑制剂的情况下，CA神经元的分化仅适度降低。独立于MapK，BMP 4诱导Smad1从细胞质易位至细胞核，并诱导dHAND（一种CA神经元分化所需的DNA结合蛋白）的转录。数据表明，CEE衍生因子和BMP4通过独立的信号通路支持CA神经元的分化。
