美国华盛顿大学医学院研究人员发现，神经纤维瘤1型（neurofibromatosis 1）基因NF1是脑早期发育的关键基因。NF1通过c-AMP依赖和Ras依赖的两种信号机制，调节神经角质前体细胞（neuroglial progenitor）分别分化为神经元和神经角质细胞。相关结果发表在10月11日Cell Stem Cell上。
美国有10万多名患有神经纤维瘤1型疾病的患者。15%-20%患者的脑瘤来自于星形角质细胞的突变，而60%-70%患者中认知性障碍则由于神经元病变。
两种症状随机或同时发生的现象，使得科学家迷惑不解——因为单个基因的突变影响到两种不同的细胞表型。神经胶质细胞主要提供支持，保护和滋润神经元的作用，而神经元则通过相互交流处理思维和记忆。
研究人员培育出一种小鼠系，这种小鼠可选择性关闭其体内神经干细胞中与人类NF-1相对应的基因。研究发现，NF1表达蛋白神经纤维瘤素Nf1参与两条信号传导途径，即c-AMP依赖途径和Ras依赖途径，从而使得神经纤维瘤素可调控两种细胞的发育。通过Ras依赖途径对星形胶质细胞的发育必不可少，但对神经元细胞的发育则并不必须。反过来，c-AMP依赖途径则对神经元细胞的发育至关重要。
研究人员提示，对神经纤维瘤的治疗可以通过双重途径展开。同时，因为在解剖学上，神经纤维瘤1型病人脑部并没有非常明显的结构缺陷，对该Nf1小鼠系的研究将提供相关问题所在，从而可以更好理解与认知障碍关联的神经纤维瘤1型疾病。（生命科学专辑）
王小理 编译自 http://www.eurekalert.org/pub_releases/2007-11/wuis-cgd111307.php
原始出处:
Cell Stem Cell, Vol 1, 443-457, 11 October 2007
Article
Neurofibromatosis-1 Regulates Neuronal and Glial Cell Differentiation from Neuroglial Progenitors In Vivo by Both cAMP- and Ras-Dependent Mechanisms
Balazs Hegedus,1 Biplab Dasgupta,1,3 Jung Eun Shin,1 Ryan J. Emnett,1 Elizabeth K. Hart-Mahon,1 Lynda Elghazi,2 Ernesto Bernal-Mizrachi,2 and David H. Gutmann1,
1 Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA
2 Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Corresponding author
David H. Gutmann
gutmannd@wustl.edu
Individuals with neurofibromatosis type 1 (NF1) develop abnormalities of both neuronal and glial cell lineages, suggesting that the NF1 protein neurofibromin is an essential regulator of neuroglial progenitor function. In this regard, Nf1-deficient embryonic telencephalic neurospheres exhibit increased self-renewal and prolonged survival as explants in vivo. Using a newly developed brain lipid binding protein (BLBP)-Cre mouse strain to study the role of neurofibromin in neural progenitor cell function in the intact animal, we now show that neuroglial progenitor Nf1 inactivation results in increased glial lineage proliferation and abnormal neuronal differentiation in vivo. Whereas the glial cell lineage abnormalities are recapitulated by activated Ras or Akt expression in vivo, the neuronal abnormalities were Ras- and Akt independent and reflected impaired cAMP generation in Nf1-deficient cells in vivo and in vitro. Together, these findings demonstrate that neurofibromin is required for normal glial and neuronal development involving separable Ras-dependent and cAMP-dependent mechanisms.
