A Reciprocal Cell–Cell Interaction Mediated by NT-3 and Neuregulins Controls the Early Survival and Development of Sympathetic Neuroblasts

A Reciprocal Cell–Cell Interaction Mediated by NT-3 and Neuregulins Controls the Early Survival and Development of Sympathetic Neuroblasts
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DOI:
10.1016/s0896-6273(00)80071-9
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发表时间:
1996-03
期刊:
影响因子:
16.2
通讯作者:
J. Verdi;J. Verdi;A. Groves;I. Fariñas;K. Jones;M. Marchionni;L. Reichardt;D. Anderson;D. Anderson
J. Verdi;J. Verdi;A. Groves;I. Fariñas;K. Jones;M. Marchionni;L. Reichardt;D. Anderson;D. Anderson
中科院分区:
医学1区
文献类型:
--
作者:
J. Verdi;J. Verdi;A. Groves;I. Fariñas;K. Jones;M. Marchionni;L. Reichardt;D. Anderson;D. Anderson

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神经营养因子3(NT-3)可在交感神经母细胞依赖神经生长因子之前支持其存活。我们发现,NT-3在体内是由胚胎交感神经节附近的非神经细胞产生的。NT-3mRNA由这些非神经细胞在体外产生,并受到血小板衍生生长因子、睫状神经营养因子和神经胶质生长因子2(一种神经调节蛋白)的上调。非神经细胞条件培养液可促进交感神经母细胞存活并诱导TrkA的表达,这种活性可被抗NT-3抗体阻断。神经母细胞也能促进非神经细胞产生NT-3。神经母细胞合成几种形式的神经调节蛋白,神经调节蛋白的抗体减弱了神经母细胞对非神经细胞的影响。这些数据表明了一种细胞-细胞的相互作用,在这种作用中,神经母细胞来源的中性调节蛋白促进了邻近非神经元细胞产生NT-3,进而促进了神经母细胞的存活和进一步分化。
Neurotrophin 3 (NT-3) can support the survival of some embryonic sympathetic neuroblasts before they become nerve growth factor dependent. We show that NT-3 is produced in vivo by nonneuronal cells neighboring embryonic sympathetic ganglia. NT-3 mRNA is produced by these nonneuronal cells in vitro and is up-regulated by platelet-derived growth factor, ciliary neurotrophic factor, and glial growth factor 2 (a neuregulin). Nonneuronal cell–conditioned medium promotes survival and induces TrkA expression in isolated sympathetic neuroblasts, and this activity is blocked by anti-NT-3 antibody. Neuroblasts also enhance NT-3 production by nonneuronal cells. Neuroblasts synthesize several forms of neuregulin, and antibodies to neuregulin attenuate the effect of the neuroblasts on the nonneuronal cells. These data suggest a reciprocal cell–cell interaction, in which neuroblast-derived neuregulins promote NT-3 production by neighboring nonneuronal cells, which in turn promotes neuroblast survival and further differentiation.