Function of Oncogene Mycn in Adult Neurogenesis and Oligodendrogenesis.
Function of Oncogene Mycn in Adult Neurogenesis and Oligodendrogenesis.
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DOI：
10.1007/s12035-021-02584-7
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发表时间：
2022-01
影响因子：
5.1
通讯作者：
Guan Z
中科院分区：
文献类型：
--
作者：
Chen J;Guan Z
人MYCN是在神经母细胞瘤和许多其他肿瘤中扩增的癌基因。人和小鼠的MYCN基因在胚胎脑发育中都是重要的，但它们在成年健康神经系统中的功能完全未知。在此，我们使用Mycn-eGFP小鼠和定量RT-PCR，发现Mycn在年轻成年小鼠的特定脑区表达，包括脑室下区（SVZ），颗粒下区（SGZ），嗅球（OB），胼胝体下区（SCZ）和胼胝体（CC）。通过免疫组织化学（IHC），我们发现许多表达Mycn的细胞表达成神经细胞标记物doublecortin（DCX）和增殖标记物Ki 67。使用Dcx-creER和Mki 67-creER小鼠系，我们对表达Dcx的神经母细胞和表达Mki 67的增殖细胞进行了命运定位，沿着从成年小鼠的这些细胞中删除Mycn。我们发现，从成年成神经细胞或增殖细胞中敲除Mycn显著降低了SVZ、SGZ、OB、SCZ和CC中细胞的增殖。我们还证明了SGZ中Mycn缺陷型神经母细胞比野生型神经母细胞成熟得更快，并且与野生型相比，Mycn缺陷型增殖细胞更有可能在SVZ，SGZ，OB，SCZ和CC中存活。因此，我们的研究结果表明，除了在神经系统中引起肿瘤外，癌基因Mycn在成年健康大脑的神经发生和少突胶质细胞发生中具有至关重要的功能。在线版本包含补充材料，可通过10.1007/s12035-021-02584-7获得。
Human MYCN is an oncogene amplified in neuroblastoma and many other tumors. Both human MYCN and mouse Mycn genes are important in embryonic brain development, but their functions in adult healthy nerve system are completely unknown. Here, with Mycn-eGFP mice and quantitative RT-PCR, we found that Mycn was expressed in specific brain regions of young adult mice, including subventricular zone (SVZ), subgranular zone (SGZ), olfactory bulb (OB), subcallosal zone (SCZ), and corpus callosum (CC). With immunohistochemistry (IHC), we found that many Mycn-expressing cells expressed neuroblast marker doublecortin (DCX) and proliferation marker Ki67. With Dcx-creER and Mki67-creER mouse lines, we fate mapped Dcx-expressing neuroblasts and Mki67-expressing proliferation cells, along with deleting Mycn from these cells in adult mice. We found that knocking out Mycn from adult neuroblasts or proliferating cells significantly reduced cells in proliferation in SVZ, SGZ, OB, SCZ, and CC. We also demonstrated that the Mycn-deficient neuroblasts in SGZ matured quicker than wild-type neuroblasts, and that Mycn-deficient proliferating cells were more likely to survive in SVZ, SGZ, OB, SCZ, and CC compared to wild type. Thus, our results demonstrate that, in addition to causing tumors in the nervous system, oncogene Mycn has a crucial function in neurogenesis and oligodendrogenesis in adult healthy brain. The online version contains supplementary material available at 10.1007/s12035-021-02584-7.
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影响因子：
3.5
作者：
Ruiz-Pérez MV;Henley AB;Arsenian-Henriksson M
通讯作者：
Arsenian-Henriksson M
影响因子：
3.7
作者：
Mobley BC;Kwon M;Kraemer BR;Hickman FE;Qiao J;Chung DH;Carter BD
通讯作者：
Carter BD
影响因子：
8
作者：
Caron, Nicolas;Genin, Emmanuelle C.;Malgrange, Brigitte
通讯作者：
Malgrange, Brigitte
影响因子：
5.3
作者：
Magri, Laura;Swiss, Victoria A.;Casaccia, Patrizia
通讯作者：
Casaccia, Patrizia
影响因子：
6.2
作者：
Nobs, Lionel;Nestel, Sigrun;Atanasoski, Suzana
通讯作者：
Atanasoski, Suzana