Neuregulin-1 increases the proliferation of neuronal progenitors from embryonic neural stem cells
Neuregulin-1 increases the proliferation of neuronal progenitors from embryonic neural stem cells
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DOI：
10.1016/j.ydbio.2005.04.038
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发表时间：
2005-07-15
影响因子：
2.7
通讯作者：
Fischbach, GD
中科院分区：
文献类型：
--
作者：
Liu, Y;Ford, BD;Fischbach, GD
神经调节蛋白是在发育中的脑和在成年动物中继续经历神经发生的脑区域中表达的蛋白质家族。我们研究了神经调节素对从El I小鼠端脑分离的胚胎神经干细胞（NSCs）的影响。用神经调节蛋白1-β 1（NRG-1（177-244））的EGF样结构域处理碱性成纤维细胞生长因子（bFGF）扩增的神经球培养物，导致溴脱氧尿苷（BrDU）标记的细胞增加4倍，表明NRG-1刺激增殖。大多数BrdU阳性细胞与针对MAP 2的抗体共标记，表明增殖细胞是神经元细胞。GFAP或O 4阳性细胞未见BrDU标记。在NRG-1处理的培养物中，许多MAP 2阳性细胞与抗巢蛋白抗体共标记，表明这些细胞是神经元限制性祖细胞（NRP）。在对照培养物中观察到很少的MAP 2/巢蛋白阳性细胞。NRG-1处理的培养物中神经元细胞数量的增加是由于MAP 2阳性细胞的增殖增加，而不是细胞存活或命运决定的调节。这些结果表明神经调节蛋白对NRP具有促有丝分裂作用，因此内源性神经调节蛋白可能在中枢神经系统神经发生过程中发挥重要作用。(c)2005年爱思唯尔公司All rights reserved.
Neuregulins are a family of proteins expressed in the developing brain and in brain regions that continue to undergo neurogenesis in adult animals. We investigated the effects of neuregulins on embryonic neural stem cells (NSCs) isolated from El I mouse telencephalon. Treatment of basic fibroblast growth factor (bFGF)-expanded neurosphere cultures with the EGF-like domain of neuregulin1-beta 1 (NRG-1(177-244)) resulted in a 4-fold increase of bromodeoxyuridine (BrDU)-labeled cells, suggesting that NRG-1 stimulated proliferation. The majority of the BrdU-positive cells co-labeled with an antibody against MAP2, indicating that the proliferating cells were neuronal. No BrDU labeling was seen in GFAP- or O4-positive cells. In NRG-1-treated cultures, many of the MAP2-positive cells co-labeled with an anti-nestin antibody, suggesting that these cells are neuron-restricted progenitors (NRPs). Few MAP2/nestin-positive cells were seen in control cultures. The increase in the number of neuronal cells in NRG-1-treated cultures was due to increased proliferation of MAP2-positive cells rather than the regulation of cell survival or fate determination. These results suggest that neuregulins are mitogenic to NRPs, thus endogenous neuregulins may play important roles during CNS neurogenesis. (c) 2005 Elsevier Inc. All rights reserved.