Ochoa A, Domenzáin C, Clapp C, Martínez de la Escalera G
Neurobiology Center, National University of México, Juriquilla, Querétaro.
J Neurosci Res. 1997 Sep 15;49(6):739-49. doi: 10.1002/(SICI)1097-4547(19970915)49:6<739::AID-JNR8>3.0.CO;2-8.
Recent studies in several neuronal lineages suggest that extrinsic factors such as polypeptide growth factors regulate various stages of neuronal development, from initial commitment of multipotent progenitors to induction of specific gene expression that is characteristic of terminal neuronal differentiation. In the present study, immortalized hypothalamic neurons of the GT1-1 lineage were used to analyze proliferative, as well as morphological and molecular differentiation actions of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factor-I (IGF-I). These effects were compared with those induced by specific activators of protein kinase A and C pathways, which potently inhibited cell proliferation and gonadotropin-releasing hormone (GnRH) gene expression, but stimulated morphological neuronal maturation as determined by the length and number of neurite outgrowth. bFGF exerted a broad spectrum of stimulatory effects, increasing the rate of proliferation measured both by the incorporation of 3H-thymidine and by cell number, and parameters of terminal differentiation, such as neurite outgrowth and induction of gene expression. bFGF stimulated the expression of the hybrid transgene-containing portions of the rat GnRH promoter. In contrast, EGF, TGF-alpha, and IGF-I inhibited cell proliferation, while having subtle effects on neurite outgrowth. Thus, GT1-1 cells appear to be differentially responsive to distinct neurotrophic factors, providing a model for studying the specific effects of neurotrophic factors on functional differentiation, migration, and connectivity of hypothalamic neurons.
最近在多个神经元谱系中的研究表明，诸如多肽生长因子等外在因素可调节神经元发育的各个阶段，从多能祖细胞的初始定向到诱导终末神经元分化所特有的特定基因表达。在本研究中，使用GT1-1谱系的永生化下丘脑神经元来分析碱性成纤维细胞生长因子（bFGF）、表皮生长因子（EGF）、转化生长因子-α（TGF-α）和胰岛素样生长因子-I（IGF-I）的增殖以及形态和分子分化作用。将这些效应与蛋白激酶A和C途径的特异性激活剂所诱导的效应进行比较，蛋白激酶A和C途径的特异性激活剂可有效抑制细胞增殖和促性腺激素释放激素（GnRH）基因表达，但可刺激由神经突生长的长度和数量所确定的神经元形态成熟。bFGF发挥了广泛的刺激作用，通过3H-胸腺嘧啶掺入和细胞数量测量均增加了增殖速率，并增加了终末分化参数，如神经突生长和基因表达诱导。bFGF刺激了含有大鼠GnRH启动子部分的杂交转基因的表达。相比之下，EGF、TGF-α和IGF-I抑制细胞增殖，而对神经突生长有细微影响。因此，GT1-1细胞似乎对不同的神经营养因子有不同的反应，为研究神经营养因子对下丘脑神经元功能分化、迁移和连接的特定作用提供了一个模型。
