Hsieh Yen-Che, Chiang Ming-Chang, Huang Yin-Cheng, Yeh Tu-Hsueh, Shih Hung-Yu, Liu Han-Fang, Chen Hao-Yuan, Wang Chien-Ping, Cheng Yi-Chuan
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Life Science, Fu Jen Catholic University, New Taipei City, Taiwan.
Dev Dyn. 2018 Dec;247(12):1264-1275. doi: 10.1002/dvdy.24683. Epub 2018 Nov 26.
Many molecules and signaling pathways involved in neural development play a role in neurodegenerative diseases and brain tumor progression. Peroxisome proliferator-activated receptor (PPAR) proteins regulate the differentiation of tissues and the progression of many diseases. However, the role of these proteins in neural development is unclear.
We examined the function of Pparα in the neural development of zebrafish. Two duplicate paralogs for mammalian PPARA/Ppara, namely pparaa and pparab, are present in the zebrafish genome. Both pparaa and pparab are expressed in the developing central nervous system in zebrafish embryos. Inhibiting the function of Pparα by using either the PPARα/Pparα antagonist GW6471 or pparaa or pparab truncated constructs produced identical phenotypes, which were sufficient to reduce the proliferation of neuronal and glial precursor cells without affecting the formation of neural progenitors.
We demonstrated that both Pparαa and Pparαb proteins are essential regulators of the proliferation of neuronal and glial precursors. This study provides a better understanding of the functions of PPARα/Pparα in neural development and further expands our knowledge of the potential role of PPARα/Pparα in neurological disorders and brain tumors. Developmental Dynamics 247:1264-1275, 2018. © 2018 Wiley Periodicals, Inc.
许多参与神经发育的分子和信号通路在神经退行性疾病和脑肿瘤进展中发挥作用。过氧化物酶体增殖物激活受体(PPAR)蛋白调节组织分化和多种疾病的进展。然而,这些蛋白在神经发育中的作用尚不清楚。
我们研究了斑马鱼中Pparα在神经发育中的功能。斑马鱼基因组中存在哺乳动物PPARA/Ppara的两个重复旁系同源基因,即pparaa和pparab。pparaa和pparab在斑马鱼胚胎发育中的中枢神经系统中均有表达。使用PPARα/Pparα拮抗剂GW6471或pparaa或pparab截短构建体抑制Pparα的功能产生了相同的表型,这些表型足以减少神经元和神经胶质前体细胞的增殖,而不影响神经祖细胞的形成。
我们证明Pparαa和Pparαb蛋白都是神经元和神经胶质前体细胞增殖的重要调节因子。这项研究有助于更好地理解PPARα/Pparα在神经发育中的功能,并进一步扩展我们对PPARα/Pparα在神经疾病和脑肿瘤中潜在作用的认识。《发育动力学》247:1264 - 1275,2018年。©2018威利期刊公司。