骨形态发生蛋白（BMP）信号传导在胚胎大鼠中枢神经系统干细胞中启动神经嵴分化程序。

BMP signaling initiates a neural crest differentiation program in embryonic rat CNS stem cells.

作者信息

Gajavelli Shyam, Wood Patrick M, Pennica Diane, Whittemore Scott R, Tsoulfas Pantelis

机构信息

Department of Neurosurgery, The Miami Project to Cure Paralysis, University of Miami School of Medicine, FL 33136, USA.

出版信息

Exp Neurol. 2004 Aug;188(2):205-23. doi: 10.1016/j.expneurol.2004.03.026.

DOI:10.1016/j.expneurol.2004.03.026

PMID:15246821

Abstract

Bone morphogenetic proteins (BMPs) have an important role in neuronal and astrocytic differentiation of embryonic and adult neural stem cells (NSCs). Here, we show that BMP6, BMP7, GDF5, and GDF6 instructively differentiate E12, E14, and E17 rat cortical NSCs into a variety of neural crest lineages. Clonal analysis shows that BMP7-treated NSCs develop mostly into smooth muscle and peripheral glia. We observed a rapid induction of premigratory neural crest markers like p75NTR, and AP-2 alpha followed by Msx1, Msx2, and Slug, transcription factors that participate in neural crest development. These results suggest that NSCs cultured in vitro in the presence of FGF2 display expanded developmental potential.

摘要

骨形态发生蛋白（BMPs）在胚胎和成年神经干细胞（NSCs）的神经元和星形胶质细胞分化中起重要作用。在此，我们表明BMP6、BMP7、生长分化因子5（GDF5）和生长分化因子6（GDF6）可诱导E12、E14和E17大鼠皮质神经干细胞分化为多种神经嵴谱系。克隆分析表明，经BMP7处理的神经干细胞大多发育为平滑肌和外周神经胶质细胞。我们观察到迁移前神经嵴标志物如p75神经营养因子受体（p75NTR）和AP - 2α迅速诱导，随后是参与神经嵴发育的转录因子Msx1、Msx2和Slug。这些结果表明，在成纤维细胞生长因子2（FGF2）存在下体外培养的神经干细胞具有扩展的发育潜能。