Antonacci Simona, Forand Daniel, Wolf Margaret, Tyus Courtney, Barney Julia, Kellogg Leah, Simon Margo A, Kerr Genevieve, Wells Kristen L, Younes Serena, Mortimer Nathan T, Olesnicky Eugenia C, Killian Darrell J
Department of Molecular Biology, Colorado College, Colorado Springs, Colorado 80903.
Department of Biology, University of Colorado Colorado Springs, Colorado Springs, Colorado 80918.
G3 (Bethesda). 2015 Feb 10;5(4):639-53. doi: 10.1534/g3.115.017327.
The regulation of dendritic branching is critical for sensory reception, cell-cell communication within the nervous system, learning, memory, and behavior. Defects in dendrite morphology are associated with several neurologic disorders; thus, an understanding of the molecular mechanisms that govern dendrite morphogenesis is important. Recent investigations of dendrite morphogenesis have highlighted the importance of gene regulation at the posttranscriptional level. Because RNA-binding proteins mediate many posttranscriptional mechanisms, we decided to investigate the extent to which conserved RNA-binding proteins contribute to dendrite morphogenesis across phyla. Here we identify a core set of RNA-binding proteins that are important for dendrite morphogenesis in the PVD multidendritic sensory neuron in Caenorhabditis elegans. Homologs of each of these genes were previously identified as important in the Drosophila melanogaster dendritic arborization sensory neurons. Our results suggest that RNA processing, mRNA localization, mRNA stability, and translational control are all important mechanisms that contribute to dendrite morphogenesis, and we present a conserved set of RNA-binding proteins that regulate these processes in diverse animal species. Furthermore, homologs of these genes are expressed in the human brain, suggesting that these RNA-binding proteins are candidate regulators of dendrite development in humans.
树突分支的调控对于感觉接收、神经系统内的细胞间通讯、学习、记忆和行为至关重要。树突形态的缺陷与多种神经系统疾病相关;因此,了解控制树突形态发生的分子机制很重要。最近对树突形态发生的研究突出了转录后水平基因调控的重要性。由于RNA结合蛋白介导许多转录后机制,我们决定研究保守的RNA结合蛋白在多大程度上有助于跨门的树突形态发生。在这里,我们鉴定出一组核心的RNA结合蛋白,它们对秀丽隐杆线虫的PVD多树突感觉神经元中的树突形态发生很重要。这些基因中的每一个的同源物先前已被鉴定在果蝇的树突分支感觉神经元中很重要。我们的结果表明,RNA加工、mRNA定位、mRNA稳定性和翻译控制都是有助于树突形态发生的重要机制,并且我们提出了一组保守的RNA结合蛋白,它们在不同动物物种中调节这些过程。此外,这些基因的同源物在人类大脑中表达,表明这些RNA结合蛋白是人类树突发育的候选调节因子。