The Notch co-repressor protein NKAP is highly expressed in adult mouse subventricular zone neural progenitor cells

The Notch co-repressor protein NKAP is highly expressed in adult mouse subventricular zone neural progenitor cells
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DOI:
10.1016/j.neuroscience.2014.02.019
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发表时间:
2014-04
期刊:
影响因子:
3.3
通讯作者:
M. M. Worlitzer-M.;J. Schwamborn
M. M. Worlitzer-M.;J. Schwamborn
中科院分区:
医学3区
文献类型:
--
作者:
M. M. Worlitzer-M.;J. Schwamborn

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在成年哺乳动物的大脑中,维持着神经干细胞的壁龛,这使得稳定的神经发生成为可能。这一过程受到多种生态位因素的严格调控,包括Notch和NF-κB信号。已有研究表明,在T细胞发育过程中,核转录因子κB激活蛋白(NKAP)通过结合CIR和募集HDAC3而扮演Notch型共抑制因子的角色,进而调节NF-κB依赖的转录。在这里,我们提供了NKAP在成年哺乳动物大脑的神经源性细胞中表达的第一个证据。NKAP高表达于Mash1+转运放大细胞和PSA-NCAM+移行性神经母细胞,分布于脑室下带(SVZ)、吻侧移行流(RMS)以及海马区。我们进一步表明,在RMS过程中,NKAP的表达水平下调。最终,大多数分化的细胞在嗅球(OB)和胼胝体中只显示低水平的NKAP表达。最后,OB、海马和丘脑中的成熟神经元的大亚群高水平表达NKAP,这表明NKAP在SVZ前体细胞之外还有额外的作用。
In the adult mammalian brain niches for neural stem cells are maintained, which enable a steady-state neurogenesis. This process is tightly regulated by multiple niche factors, including Notch and NF-κB signaling. The NF-κB-activating-protein (NKAP) has previously been shown to act as Notch co-repressor component by binding CIR and recruiting HDAC3 in T-cell development and furthermore to regulate NF-κB-dependent transcription. Here, we provide first evidence for the expression of NKAP in neurogenic cells of the adult mammalian brain. NKAP is highly expressed in Mash1+transit amplifying cells and PSA-NCAM+migrating neuroblasts throughout the subventricular zone (SVZ) and the rostral migratory stream (RMS), as well as in the hippocampus. We further show that NKAP expression levels are downregulated during the course of the RMS. Eventually, most differentiated cells in the olfactory bulb (OB) and the corpus callosum only display low levels of NKAP expression. Finally, large subsets of mature neurons in the OB, the hippocampus and the thalamus express NKAP at high levels, suggesting an additional role of NKAP outside of SVZ progenitor cells.