Anuppalle Mrudhula, Maddirevula Sateesh, Kumar Ajeet, Huh Tae-Lin, Choe Joonho, Rhee Myungchull
Department of Life Science, BK21 Plus Program, Graduate School, Chungnam National University, Daejeon 34134, South Korea.
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 3354, Saudi Arabia.
Gene Expr Patterns. 2017 Jan;23-24:45-51. doi: 10.1016/j.gep.2017.03.002. Epub 2017 Mar 11.
PRUNE2 has been identified as a susceptible gene for Alzheimer's disease and a marker for leiomyosarcomas. Isoforms of Prune2 regulate neuronal cell differentiation and synaptogenesis. Although expression pattern of Prune2 has been reported in the murine brain, its expression patterns and regulation along vertebrate embryogenesis remain to be further investigated. We thus defined the expression profiles and transcriptional regulation of prune2 in zebrafish embryos. prune2 exhibits maternal expression, but is increased in later embryonic stages, and expressed in the telencephalon, epiphysis cluster, nucleus of the tract of the post optic commissure, spinal cord, cerebellum, tegmentum, anterior lateral line ganglion, posterior lateral line ganglion and rhombomeres 2 through 5. Two color WISH with a post-mitotic neuron specific marker, huC defined that prune2 is expressed in the post mitotic neurons. The level of prune2 transcripts is upregulated in Notch signaling homozygous mutant, mib1(mib), indicating that Notch signaling regulates transcription of prune2. Interestingly, in silico analysis of prune2 promoter found retinoic acid (RA) response elements (AGGTCAcaTGACCA) located at -3 to -16 relative to the first exon. It turned out that RA signaling altered the expression pattern of prune2 in the hindbrain. We further propose that Prune2 might be a putative regulator for CNS development in zebrafish embryogenesis.
PRUNE2已被确定为阿尔茨海默病的易感基因和平滑肌肉瘤的标志物。Prune2的异构体调节神经元细胞分化和突触形成。尽管Prune2在小鼠大脑中的表达模式已有报道，但其在脊椎动物胚胎发育过程中的表达模式和调控仍有待进一步研究。因此，我们确定了斑马鱼胚胎中prune2的表达谱和转录调控。prune2表现出母源表达，但在胚胎后期增加，并在端脑、松果体簇、视交叉后束核、脊髓、小脑、被盖、前侧线神经节、后侧线神经节以及菱脑节2至5中表达。用有丝分裂后神经元特异性标记物huC进行双色原位杂交表明，prune2在有丝分裂后神经元中表达。prune2转录本水平在Notch信号通路纯合突变体mib1（mib）中上调，表明Notch信号通路调节prune2的转录。有趣的是，对prune2启动子的计算机分析发现，视黄酸（RA）反应元件（AGGTCAcaTGACCA）位于相对于第一个外显子的-3至-16处。结果表明，RA信号通路改变了prune2在后脑的表达模式。我们进一步提出，Prune2可能是斑马鱼胚胎发育过程中中枢神经系统发育的一个假定调节因子。
