Worlitzer M M A, Schwamborn J C
Westfälische Wilhelms-Universität Münster, ZMBE, Institute of Cell Biology, Stem Cell Biology and Regeneration Group, Von-Esmarch-Straße 56, 48149 Münster, Germany; Interdisciplinary Center for Clinical Research (IZKF) Münster, Germany.
Westfälische Wilhelms-Universität Münster, ZMBE, Institute of Cell Biology, Stem Cell Biology and Regeneration Group, Von-Esmarch-Straße 56, 48149 Münster, Germany; Interdisciplinary Center for Clinical Research (IZKF) Münster, Germany; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval, Luxembourg.
Neuroscience. 2014 Apr 25;266:138-49. doi: 10.1016/j.neuroscience.2014.02.019. Epub 2014 Feb 27.
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.
在成年哺乳动物大脑中,神经干细胞龛得以维持,从而实现稳态神经发生。这一过程受到多种龛因子的严格调控,包括Notch和NF-κB信号通路。此前研究表明,NF-κB激活蛋白(NKAP)在T细胞发育过程中通过结合CIR并招募HDAC3,作为Notch共抑制因子发挥作用,此外还能调节NF-κB依赖的转录。在此,我们首次提供了NKAP在成年哺乳动物大脑神经源性细胞中表达的证据。NKAP在整个脑室下区(SVZ)和嘴侧迁移流(RMS)中的Mash1(+) 过渡增殖细胞和PSA-NCAM(+) 迁移神经母细胞以及海马体中高度表达。我们进一步表明,在RMS进程中,NKAP表达水平下调。最终,嗅球(OB)和胼胝体中的大多数分化细胞仅表现出低水平的NKAP表达。最后,OB、海马体和丘脑中的大量成熟神经元亚群高水平表达NKAP,表明NKAP在SVZ祖细胞之外还有其他作用。