Drosophila Hrp48 Is Required for Mushroom Body Axon Growth, Branching and Guidance.
Drosophila Hrp48 Is Required for Mushroom Body Axon Growth, Branching and Guidance.
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DOI：
10.1371/journal.pone.0136610
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Besse F
中科院分区：
文献类型：
--
作者：
Bruckert H;Marchetti G;Ramialison M;Besse F
RNA结合蛋白在mRNA上组装以控制其生命周期的每一个步骤，从核剪接到细胞质定位，稳定或翻译。与RNA结合蛋白在神经元成熟和功能中的重要作用一致，这类蛋白质，特别是hnRNP家族成员中的突变与神经系统疾病相关。然而，迄今为止，hnRNP在体内神经元发育过程中的生理功能仍然探索不足。在这里，我们已经调查了果蝇Hrp 48的作用，果蝇同源的哺乳动物hnRNP A2/B1，在中枢神经系统发育。使用突变条件的组合，我们表明，hrp 48是所需的形成，生长和指导的轴突分支在蘑菇体神经元。此外，我们的研究结果表明，hrp 48失活诱导蘑菇体背侧轴突分支的过度延伸，女性比男性具有显着更高的延伸率。最后，如免疫定位研究所示，Hrp 48仅限于蘑菇体神经元细胞体，从幼虫期到成年期，它在细胞质中积累。总而言之，我们的数据提供了一个关键的hnRNP Hrp 48在神经系统发育过程中的轴突导向和分支的多个方面在体内的作用的证据。它们还表明在性非二态神经元结构的发育中存在隐藏的性别差异。
RNA binding proteins assemble on mRNAs to control every single step of their life cycle, from nuclear splicing to cytoplasmic localization, stabilization or translation. Consistent with an essential role of RNA binding proteins in neuronal maturation and function, mutations in this class of proteins, in particular in members of the hnRNP family, have been associated with neurological diseases. To date, however, the physiological function of hnRNPs during in vivo neuronal development has remained poorly explored. Here, we have investigated the role of Drosophila Hrp48, a fly homologue of mammalian hnRNP A2/B1, during central nervous system development. Using a combination of mutant conditions, we showed that hrp48 is required for the formation, growth and guidance of axonal branches in Mushroom Body neurons. Furthermore, our results revealed that hrp48 inactivation induces an overextension of Mushroom Body dorsal axonal branches, with a significantly higher penetrance in females than in males. Finally, as demonstrated by immunolocalization studies, Hrp48 is confined to Mushroom Body neuron cell bodies, where it accumulates in the cytoplasm from larval stages to adulthood. Altogether, our data provide evidence for a crucial in vivo role of the hnRNP Hrp48 in multiple aspects of axon guidance and branching during nervous system development. They also indicate cryptic sex differences in the development of sexually non-dimorphic neuronal structures.