MiR-124 is differentially expressed in derivatives of the sympathoadrenal cell lineage and promotes neurite elongation in chromaffin cells
MiR-124 is differentially expressed in derivatives of the sympathoadrenal cell lineage and promotes neurite elongation in chromaffin cells
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DOI：
10.1007/s00441-016-2395-9
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发表时间：
2016-04
影响因子：
3.6
通讯作者：
Stella Shtukmaster;Priyanka Narasimhan;Tehani El Faitwri;J. Stubbusch;U. Ernsberger;H. Rohrer;K. Unsicker;K. Huber
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文献类型：
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作者：
Stella Shtukmaster;Priyanka Narasimhan;Tehani El Faitwri;J. Stubbusch;U. Ernsberger;H. Rohrer;K. Unsicker;K. Huber
神经嵴来源的交感肾上腺细胞谱系产生交感神经元和肾上腺髓质的内分泌嗜铬细胞。这两种细胞类型表达的基因在很大程度上是重叠的，包括那些编码与儿茶酚胺的合成和胞吐释放相关的分子机制的基因。在它们的早期发育过程中，交感神经元和嗜铬细胞依赖于一个共享的转录因子网络，该网络控制这些共同特征的建立。尽管有许多相似之处，成熟的交感神经元和嗜铬细胞在形态和功能方面存在显着差异。最突出的是，交感神经元具有哺乳动物肾上腺嗜铬细胞中不存在的轴突。交感肾上腺细胞分化为神经细胞和内分泌细胞的分子机制仍不清楚。核糖核酸酶切割器的突变失活暗示了microRNA在这种多样化中的重要性。我们在这里表明，miR-124是可检测到的发展中的交感神经元，但没有在嗜铬细胞前体。我们进一步证明，miR-124转染到培养的嗜铬细胞时，促进神经突伸长，表明其支持在非神经元交感肾上腺细胞中建立神经元形态的能力。我们的研究结果还表明，用神经营养因子神经生长因子处理PC 12细胞导致miR-124表达上调，并且miR-124的抑制减少了神经生长因子诱导的PC 12细胞中的神经突生长。因此，我们的数据表明，miR-124有助于在发育中的交感肾上腺细胞中建立特定的神经元特征。
The neural-crest-derived sympathoadrenal cell lineage gives rise to sympathetic neurons and to endocrine chromaffin cells of the adrenal medulla. Both cell types express a largely overlapping set of genes, including those coding for the molecular machinery related to the synthesis and exocytotic release of catecholamines. During their early development, sympathetic neurons and chromaffin cells rely on a shared transcription factor network that controls the establishment of these common features. Despite many similarities, mature sympathetic neurons and chromaffin cells significantly differ regarding their morphology and function. Most prominently, sympathetic neurons possess axons that are absent in mammalian adrenal chromaffin cells. The molecular mechanism underlying the divergent development of sympathoadrenal cells into neuronal and endocrine cells remains elusive. Mutational inactivation of the ribonuclease dicer hints at the importance of microRNAs in this diversification. We show here that miR-124 is detectable in developing sympathetic neurons but absent in chromaffin cell precursors. We further demonstrate that miR-124 promotes neurite elongation when transfected into cultured chromaffin cells indicating its capability to support the establishment of a neuronal morphology in non-neuronal sympathoadrenal cells. Our results also show that treatment of PC12 cells with the neurotrophin nerve growth factor leads to an upregulation of miR-124 expression and that inhibition of miR-124 reduces nerve-growth-factor-induced neurite outgrowth in PC12 cells. Thus, our data indicate that miR-124 contributes to the establishment of specific neuronal features in developing sympathoadrenal cells.