Sudden reduction of miRNAs during embryonic development-- cohort, buffered regulation of miRNA in Dorsal Root Ganglion

Micro RNAs (miRNA) are short, endogenous non-coding RNAs, they function via base pairing with complementary sequences with their targets. With the current advance in modern technologies including Next Generation Sequencing, miRNAs have rapidly emerged as important regulators in various functions in cell proliferation, differentiation, cell death and metabolisms. miRNAs showed specifically important roles in central nerve system development with specific temporal spatial regulation, such as neuronal cell proliferation, neuronal differentiation, cell fate determination, axon outgrowth, dendritogenesis, synaptogenesis, and gliogenesis, neuronal guidance to form neuronal circuits. In this study, we will first focus on how microRNA regulates neuronal specification, proliferation and differentiation by investigating microRNA profiling in Dorsal Root Ganglion (DRG) at different embryonic stages both in chickens and mice. Second, we will investigate how the microRNA expression correlates with important transcription factors and neurotrophic factor receptors during the neuron cell specification, such as Runx3, TrkC. Third, we study the regulated miRNA targets and their impact on neurogenesis and development. Last, we will study how conserved roles of miRNA between mouse and chicken in the neuro-specification. We found dramatic reduction of large amount miRNA during specific embryonic stage. Their target genes overrepresent dentrites, synaps and neurogenesis genes, as well as genes largely involved in transcription. The study shows the importance of miRNA in neuronal development, and they function in cohort, buffered, flexible manner. Spatial and temopary expression of miRNA of Dorsal Root Ganglion at embryonic developmental stages, and the expression of miRNA after treatment with different neurotrophins, transcription activators and neurotransmitters.微小RNA（microRNAs，简称miRNA）是一类短小的内源性非编码RNA，通过与靶基因的互补序列碱基配对发挥功能。随着包括下一代测序技术在内的现代生物技术的发展，miRNA已迅速成为细胞增殖、分化、细胞死亡及代谢等多种生理过程的重要调控因子。miRNA在中枢神经系统发育中发挥尤为关键的作用，且具有严格的时空特异性调控模式，参与神经元增殖、神经元分化、细胞命运决定、轴突生长、树突发生、突触发生、胶质细胞发生以及神经元导向以形成神经环路等过程。本研究首先将聚焦于miRNA如何调控神经元特化、增殖与分化，具体通过分析鸡和小鼠不同胚胎时期背根神经节（Dorsal Root Ganglion，简称DRG）的miRNA表达谱展开。其次，本研究将探究在神经元特化过程中，miRNA的表达与关键转录因子及神经营养因子受体（如Runx3、TrkC）之间的关联。第三，本研究将分析受miRNA调控的靶基因及其对神经发生与发育的影响。最后，本研究将探讨miRNA在小鼠与鸡的神经元特化过程中所具有的保守性功能。我们发现，在特定胚胎阶段，大量miRNA的表达水平出现显著下调。这些miRNA的靶基因显著富集于树突相关、突触相关及神经发生相关基因，同时也大量涉及转录调控相关基因。本研究证实了miRNA在神经元发育中的重要作用，其以协同、缓冲且灵活的模式行使调控功能。本研究同时涵盖了胚胎发育阶段背根神经节中miRNA的时空表达模式，以及经不同神经营养因子、转录激活剂与神经递质处理后miRNA的表达变化。