Astroglia-derived retinoic acid is a key factor in glia-induced neurogenesis
Astroglia-derived retinoic acid is a key factor in glia-induced neurogenesis
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DOI：
10.1096/fj.06-7756com
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发表时间：
2007-08-01
期刊：
影响因子：
4.8
通讯作者：
Madarasz, E.
中科院分区：
文献类型：
--
作者：
Kornyei, Z.;Gocza, E.;Madarasz, E.
星形胶质细胞是中枢神经系统中神经源性壁龛的重要组成部分。新出现的证据表明，它们是产后神经发生的关键调节因子之一。尽管星形胶质细胞已被证明具有指导干细胞采用神经元命运的潜力，但对胶质细胞衍生的指导信号的性质知之甚少。在这里，我们提出全反式维甲酸是调控神经元细胞命运承诺的最强大的形态发生分子之一，可能是指导星形胶质细胞诱导神经发生的胶质源性因子之一。根据几种互补方法获得的数据，我们发现培养的星形胶质细胞表达维甲酸生物合成的关键酶mrna，并积极生产全反式维甲酸。我们发现泛rar拮抗剂AGN193109阻断视黄酸信号传导可阻止非承诺干细胞诱导的胶质细胞诱导的神经元形成。因此，我们为维甲酸在星形胶质细胞诱导的神经元分化中的作用提供了强有力的体外证据。
Astroglial cells are essential components of the neurogenic niches within the central nervous system. Emerging evidence suggests that they are among the key regulators of postnatal neurogenesis. Although astrocytes have been demonstrated to possess the potential to instruct stem cells to adopt a neuronal fate, little is known about the nature of the glia-derived instructive signals. Here we propose that all-trans retinoic acid, one of the most powerful morphogenic molecules regulating neuronal cell fate commitment, may be one of the glia-derived factors directing astroglia-induced neurogenesis. According to data obtained from several complementary approaches, we show that cultured astrocytes express the key enzyme mRNAs of retinoic acid biosynthesis and actively produce all-trans retinoic acid. We show that blockage of retinoic acid signaling by the pan-RAR antagonist AGN193109 prevents glia-induced neuron formation by noncommitted stem cells. Therefore, we provide strong in vitro evidence for retinoic acid action in astroglia-induced neuronal differentiation.