• 第三軍醫(yī)大學(xué)新橋醫(yī)院神經(jīng)外科（重慶，400037）;

【摘要】　目的　 探討骨形成蛋白-2（bone morphogenetic protein-2，BMP-2）對室管膜前下區(qū)（anterior subventricular zone，SVZa）神經(jīng)干細(xì)胞DLX5表達(dá)的影響。　方法　 體外培養(yǎng)SVZa神經(jīng)干細(xì)胞，用BMP-2及其拮抗劑Noggin誘導(dǎo)SVZa神經(jīng)干細(xì)胞，分別用免疫熒光染色和逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)（RT-PCR）檢測DLX5表達(dá)變化。　結(jié)果　 BMP-2組SVZa神經(jīng)干細(xì)胞DLX5蛋白表達(dá)和DLX5mRNA表達(dá)水平明顯高于對照組（P lt;0.05），且該效應(yīng)能被其拮抗劑Noggin特異性地抑制。　結(jié)論　 BMP-2是DLX5上游調(diào)節(jié)基因，可促進(jìn)SVZa神經(jīng)干細(xì)胞DLX5的表達(dá)。
【Abstract】　Objective　 To investigate the effect of bone morphogenetic protein-2 (BMP-2)on expression of DLX5 of neural stem cells in anterior subventricular zone (SVZa).　Methods　 The neural stem cells of SVZa were separated and cultured in vitro, which were induced by BMP-2 and Noggin.Immunofluorescence staining and RT-PCR were employed to assay the expression of DLX5.　Results　 The percentages of expression of DLX5 protein and DLX5 mRNA in BMP-2 group were much higher than those in the control group (P lt;0.05). And this induction could be specifically blocked by Noggin.　Conclusion　 BMP-2 is an upstream gene of DLX5; BMP-2 can promote the expression of DLX5 of the neural stem cells of SVZa.

引用本文： 劉勝華,周政,劉俊,陰金波. 骨形成蛋白-2對室管膜前下區(qū)神經(jīng)干細(xì)胞DLX5表達(dá)的影響. 華西醫(yī)學(xué), 2010, 25(12): 2177-2180. doi: 復(fù)制

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2. 　Levi G, Puche AC, Mantero S, et al. The DLX5 homeodomain gene is essential for olfactory development and connectivity in the mouse[J]. Mol Cell Neruosci, 2003, 22(4): 530-543.
3. 　Long JE, Garel S, Depew MJ, et al. DLX5 regulates development of peripheral and central components of the olfactory system[J]. J Neurosci, 2003, 23(2): 568-578.
4. 　Mehler MF, Mabie PC, Zhang D, et al. Bone morphogenetic proteins in the nervous system[J]. Trends Neurosci, 1997, 20(7): 309-317.
5. 　Stull ND, Jung JW, Iacovitti L. Induction of a dopaminergic phenotype in cultured striatal neurons by bone morphogenetic proteins[J]. Brain Res Dev Brain Res, 2001, 130(1): 91-98.
6. 　Bronner-Fraser M. Molecular analysis of neural crest formation[J]. J Physiol Paris, 2002, 96(1-2): 3-8.
7. 　Gomes WA, Mehler MF, Kessler JA. Transgenic overexpression of BMP4 increases astroglial and decreases oligodendroglial lineage commitment[J]. Dev Biol, 2003, 255(1): 164-177.
8. 　Harris SE, Guo DY, Harris MA, et al. Transcriptional regulation of BMP-2 activated genes in osteoblasts using gene expression microarray analysis: role of DLX2 and DLX5 transcription factors[J]. Front Biosci, 2003, 8(4): s1249-s1265.
9. 　張治元, 楊輝, 劉仕勇, 等. BMP-2在SVZa神經(jīng)干細(xì)胞向神經(jīng)元分化的作用[J]. 第三軍醫(yī)大學(xué)學(xué)報(bào), 2003, 25(20): 1788-1791.
10. 　陳錦華, 楊輝, 尹昌林, 等. BMP2在SVZa神經(jīng)干細(xì)胞向GABA能神經(jīng)元分化中的調(diào)控作用[J]. 第三軍醫(yī)大學(xué)學(xué)報(bào), 2007, 29(8): 699-701.
11. 　辛志成, 周 政, 楊 輝, 等. SVZa 神經(jīng)干細(xì)胞誘導(dǎo)分化為多巴胺能神經(jīng)元的實(shí)驗(yàn)研究[J]. 重慶醫(yī)學(xué), 2008, 37(5): 481-483.
12. 　Panganiban G, Rubenstein JL. Developmental functions of the distal-less/DLX homeobox genes[J]. Development, 2002, 129(19): 4371-4386.
13. 　Mabie PC, Mehler MF, Kessler JA, et al. Multiple roles of bone morphogenetic protein signaling in the regulation of cortical cell number and phenotype[J]. J Neurosci, 1999, 19 (16): 7077-7088.
  1. 1. 　Perera M, Merlo GR, Verardo S, et al. Defective neuronogenesis in the absence of DLX5[J]. Mol Cell Neruosci, 2004, 25(1): 153-161.
  2. 2. 　Levi G, Puche AC, Mantero S, et al. The DLX5 homeodomain gene is essential for olfactory development and connectivity in the mouse[J]. Mol Cell Neruosci, 2003, 22(4): 530-543.
  3. 3. 　Long JE, Garel S, Depew MJ, et al. DLX5 regulates development of peripheral and central components of the olfactory system[J]. J Neurosci, 2003, 23(2): 568-578.
  4. 4. 　Mehler MF, Mabie PC, Zhang D, et al. Bone morphogenetic proteins in the nervous system[J]. Trends Neurosci, 1997, 20(7): 309-317.
  5. 5. 　Stull ND, Jung JW, Iacovitti L. Induction of a dopaminergic phenotype in cultured striatal neurons by bone morphogenetic proteins[J]. Brain Res Dev Brain Res, 2001, 130(1): 91-98.
  6. 6. 　Bronner-Fraser M. Molecular analysis of neural crest formation[J]. J Physiol Paris, 2002, 96(1-2): 3-8.
  7. 7. 　Gomes WA, Mehler MF, Kessler JA. Transgenic overexpression of BMP4 increases astroglial and decreases oligodendroglial lineage commitment[J]. Dev Biol, 2003, 255(1): 164-177.
  8. 8. 　Harris SE, Guo DY, Harris MA, et al. Transcriptional regulation of BMP-2 activated genes in osteoblasts using gene expression microarray analysis: role of DLX2 and DLX5 transcription factors[J]. Front Biosci, 2003, 8(4): s1249-s1265.
  9. 9. 　張治元, 楊輝, 劉仕勇, 等. BMP-2在SVZa神經(jīng)干細(xì)胞向神經(jīng)元分化的作用[J]. 第三軍醫(yī)大學(xué)學(xué)報(bào), 2003, 25(20): 1788-1791.
  10. 10. 　陳錦華, 楊輝, 尹昌林, 等. BMP2在SVZa神經(jīng)干細(xì)胞向GABA能神經(jīng)元分化中的調(diào)控作用[J]. 第三軍醫(yī)大學(xué)學(xué)報(bào), 2007, 29(8): 699-701.
  11. 11. 　辛志成, 周 政, 楊 輝, 等. SVZa 神經(jīng)干細(xì)胞誘導(dǎo)分化為多巴胺能神經(jīng)元的實(shí)驗(yàn)研究[J]. 重慶醫(yī)學(xué), 2008, 37(5): 481-483.
  12. 12. 　Panganiban G, Rubenstein JL. Developmental functions of the distal-less/DLX homeobox genes[J]. Development, 2002, 129(19): 4371-4386.
  13. 13. 　Mabie PC, Mehler MF, Kessler JA, et al. Multiple roles of bone morphogenetic protein signaling in the regulation of cortical cell number and phenotype[J]. J Neurosci, 1999, 19 (16): 7077-7088.