Zdhhc15b Regulates Differentiation of Diencephalic Dopaminergic Neurons in zebrafish
Zdhhc15b Regulates Differentiation of Diencephalic Dopaminergic Neurons in zebrafish
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DOI：
10.1002/jcb.25256
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发表时间：
2015-12
影响因子：
4
通讯作者：
Fen Wang;Xueran Chen;W. Shi;Linli Yao;Ming Gao;Yang Yang-Yang;A. Hao
中科院分区：
文献类型：
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作者：
Fen Wang;Xueran Chen;W. Shi;Linli Yao;Ming Gao;Yang Yang-Yang;A. Hao
天冬氨酸-组氨酸-组氨酸-半胱氨酸（DHHC）蛋白家族共有一个50个氨基酸的富含半胱氨酸的结构域，具有保守的DHHC特征基序。DHHC蛋白在几个生物过程中起着关键作用。几个DHHC家族成员已经涉及神经元分化和突触可塑性。它们功能的破坏会导致神经系统疾病。在这里，我们调查Zdhhc 15 b，DHHC家族成员，在斑马鱼神经发育中的作用。整体原位杂交（WISH）显示，zdhhc 15 b是人类ZDHHC 15的直系同源物，在斑马鱼（Danio rerio）前脑，特别是间脑中丰富。下调zdhhc 15 b导致间脑变小，成熟多巴胺能神经元（DA神经元）减少。在平均水平，突变zdhhc 15 b斑马鱼与T-迷宫测试检测到的学习行为不良相关。zdhhc 15 b的表达在DA神经元分化过程中上调，而zdhhc 15 b的敲低减少了DA神经元分化。体外培养的DA神经元的酪氨酸羟化酶（TH）免疫荧光也显示，在zdhhc 15 b敲低后，DA神经元是不成熟的。与zdhhc 15 b敲低后DA神经元数量减少一致，命运决定相关的转录因子如nurr 1，foxA 2和lmx 1a的表达也在morphant斑马鱼中减少。我们的研究结果表明，zdhhc 15 b控制DA神经元的命运决定，通过调节分化，但不是祖细胞增殖或DA神经元的存活。J.细胞。116：2980-2991，2015.© 2015威利期刊公司.
The aspartate‐histidine‐histidine‐cysteine (DHHC) protein family shares a 50‐amino acid cysteine‐rich domain with a conserved DHHC signature motif. DHHC proteins play a critical role in several biological processes. Several DHHC family members have been implicated in neuronal differentiation and synaptic plasticity. And disruptions to their function can lead to disease in the nervous system. Here, we investigate the role of Zdhhc15b, a DHHC family member, in neuro development in zebrafish. Whole‐mount in situ hybridization (WISH) revealed that zdhhc15b, an ortholog to human ZDHHC15, is abundant in zebrafish (Danio rerio) forebrain, especially in the diencephalon. Downregulation of zdhhc15b resulted in a smaller diencephalon and a reduction in mature dopaminergic neurons (DA neurons). In the meanshile, mutant zdhhc15b zebrafish was associated with poor learning behavior as detected by T‐maze testing. The expression of zdhhc15b was upregulated during DA neuronal differentiation whereas knock‐down of zdhhc15b diminished DA neuronal differentiation. Tyrosine hydroxylase (TH) immunofluorescence of cultured DA neurons in vitro also showed that DA neurons were immature following zdhhc15b knock‐down. Consistent with the decreased number of DA neurons following knock‐down of zdhhc15b, the expression of fate determination‐related transcription factors such as nurr1, foxA2, and lmx1a were also reduced in morphant zebrafish. Our results reveal that zdhhc15b controls DA neuronal fate decisions by regulating differentiation but not progenitor cell proliferation or DA neuronal survival. J. Cell. Biochem. 116: 2980–2991, 2015. © 2015 Wiley Periodicals, Inc.