Function of Oncogene Mycn in Adult Neurogenesis and Oligodendrogenesis

AbstractHumanMYCN is an oncogene amplified in neuroblastoma and many other tumors. Both humanMYCN and mouseMycn genes are important in embryonic brain development, but their functions in adult healthy nerve system are completely unknown. Here, withMycn-eGFP mice and quantitative RT-PCR, we found thatMycn 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 manyMycn-expressing cells expressed neuroblast marker doublecortin (DCX) and proliferation marker Ki67. WithDcx-creER andMki67-creER mouse lines, we fate mappedDcx-expressing neuroblasts andMki67-expressing proliferation cells, along with deletingMycn from these cells in adult mice. We found that knocking outMycn from adult neuroblasts or proliferating cells significantly reduced cells in proliferation in SVZ, SGZ, OB, SCZ, and CC. We also demonstrated that theMycn-deficient neuroblasts in SGZ matured quicker than wild-type neuroblasts, and thatMycn-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, oncogeneMycn has a crucial function in neurogenesis and oligodendrogenesis in adult healthy brain.
Source: Molecular Neurobiology - Category: Neurology Source Type: research