MANF regulates dopaminergic neuron development in larval zebrafish
MANF regulates dopaminergic neuron development in larval zebrafish
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DOI：
10.1016/j.ydbio.2012.07.030
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发表时间：
2012-10-15
影响因子：
2.7
通讯作者：
Panula, P.
中科院分区：
文献类型：
--
作者：
Chen, Y. -C.;Sundvik, M.;Panula, P.
中脑星形胶质细胞源性神经营养因子（MANF）是公认的多巴胺能神经营养因子，可保护多巴胺能神经元免受神经毒性损伤。然而，对MANF在脊椎动物发育过程中的作用知之甚少。在这里，我们报告说，MANF的表达是广泛的胚胎发育过程中，并在斑马鱼的qPCR和原位杂交分析的成年器官。用反义剪接阻断吗啉代寡核苷酸敲低MANF表达没有导致明显的异常表型。然而，MANF变形的多巴胺水平低于野生型幼虫，两个酪氨酸羟化酶基因转录本的表达水平降低，并观察到在MANF变形的间脑区域的某些组的th1和th2细胞的神经元数量减少。这些缺陷通过注射外源性manf mRNA来挽救。Manf mRNA可部分恢复Nr4a2缺陷幼虫Th1阳性细胞的减少。这些结果表明MANF参与了斑马鱼多巴胺能系统发育的调节。(c)2012 Elsevier Inc. All rights reserved.
Mesencephalic astrocyte derived neurotrophic factor (MANF) is recognized as a dopaminergic neurotrophic factor, which can protect dopaminergic neurons from neurotoxic damage. However, little is known about the function of MANF during the vertebrate development. Here, we report that MANF expression is widespread during embryonic development and in adult organs analyzed by qPCR and in situ hybridization in zebrafish. Knockdown of MANF expression with antisense splice-blocking morpholino oligonucleotides resulted in no apparent abnormal phenotype. Nevertheless, the dopamine level of MANF morphants was lower than that of the wild type larvae, the expression levels of the two tyrosine hydroxylase gene transcripts were decreased and a decrease in neuron number in certain groups of th1 and th2 cells in the diencephalon region in MANF morphants was observed. These defects were rescued by injection of exogenous manf mRNA. Strikingly, manf mRNA could partly restore the decrease of th1 positive cells in Nr4a2-deficient larvae. These results suggest that MANF is involved in the regulation of the development of dopaminergic system in zebrafish. (c) 2012 Elsevier Inc. All rights reserved.