Nestin is essential for zebrafish brain and eye development through control of progenitor cell apoptosis.
Nestin is essential for zebrafish brain and eye development through control of progenitor cell apoptosis.
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DOI：
10.1371/journal.pone.0009318
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发表时间：
2010-02-19
期刊：
影响因子：
3.7
通讯作者：
Wu KK
中科院分区：
文献类型：
--
作者：
Chen HL;Yuh CH;Wu KK
巢蛋白在发育中的脑神经前体细胞中表达。尽管Nestin被广泛用作鼻咽癌标记物，但它在胚胎发育中的功能尚不清楚。由于巢蛋白在斑马鱼中是保守的，其预测的序列与哺乳动物的巢蛋白同源物是聚在一起的，所以我们以斑马鱼为模型来研究其在胚胎发生中的作用。将巢蛋白吗啉(MO)注射到受精卵中，可引起时间和剂量依赖性的脑和眼发育缺陷。巢蛋白变异体表现出特征性的形态变化，包括小头、小眼和脑积水。组织学检查显示，后脑和中脑缩小，脑室扩张，视网膜组织不良，晶状体不发达。注射对照Nestin MO不引起脑或眼的改变。注射Nestin MO可减少鼻咽癌标志物ascl1b(achaete-scute Complex-like 1b)的表达，但不影响其分布。Nestin MO对胚胎致死、视力异常、类果蝇样3/4(神经元标记物)或OTX2(中脑神经元标记物)无影响，但严重扰乱了颅运动神经发育和轴突分布。为了确定这些发育缺陷是否是由于鼻咽癌细胞过度凋亡和/或增殖减少所致，我们用TUNEL法和吖啶橙染色分析了鼻咽癌细胞的凋亡情况，并通过BrdU掺入、增殖细胞核抗原和MCM5的表达分析了鼻咽癌细胞的增殖情况。后脑和中脑细胞过度凋亡。凋亡信号与ascl1b共定位。Nestin MO对细胞增殖标记物无明显影响。这些结果表明，巢蛋白对斑马鱼大脑和眼睛的发育是必不可少的，可能是通过控制前体细胞的凋亡来实现的。
Nestin is expressed in neural progenitor cells (NPC) of developing brain. Despite its wide use as an NPC marker, the function of nestin in embryo development is unclear. As nestin is conserved in zebrafish and its predicted sequence is clustered with the mammalian nestin orthologue, we used zebrafish as a model to investigate its role in embryogenesis. Injection of nestin morpholino (MO) into fertilized eggs induced time- and dose-dependent brain and eye developmental defects. Nestin morphants exhibited characteristic morphological changes including small head, small eyes and hydrocephalus. Histological examinations show reduced hind- and mid-brain size, dilated ventricle, poorly organized retina and underdeveloped lens. Injection of control nestin MO did not induce brain or eye changes. Nestin MO injection reduced expression of ascl1b (achaete-scute complex-like 1b), a marker of NPCs, without affecting its distribution. Nestin MO did not influence Elavl3/4 (Embryonic lethal, abnormal vision, Drosophila-like 3/4) (a neuronal marker), or otx2 (a midbrain neuronal marker), but severely perturbed cranial motor nerve development and axon distribution. To determine whether the developmental defects are due to excessive NPC apoptosis and/or reduced NPC proliferation, we analyzed apoptosis by TUNEL assay and acridine orange staining and proliferation by BrdU incorporation, pcna and mcm5 expressions. Excessive apoptosis was noted in hindbrain and midbrain cells. Apoptotic signals were colocalized with ascl1b. Proliferation markers were not significantly altered by nestin MO. These results suggest that nestin is essential for zebrafish brain and eye development probably through control of progenitor cell apoptosis.
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影响因子：
2.7
作者：
Chan, Tzu-Min;Chao, Chung-Hao;Yuh, Chiou-Hwa
通讯作者：
Yuh, Chiou-Hwa
影响因子：
--
作者：
Mahler, Julia;Driever, Wolfgang
通讯作者：
Driever, Wolfgang
影响因子：
11.4
作者：
Sahlgren, Cecilia M.;Pallari, Hanna-Mari;Eriksson, John E.
通讯作者：
Eriksson, John E.
DOI：
10.1016/s0165-3806(02)00583-7
发表时间：
2003-01-13
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Mueller, T;Wullimann, MF
通讯作者：
Wullimann, MF
影响因子：
3.4
作者：
Qiu, Guanting;Seiler, Magdalene J.;Sadda, SriniVas R.
通讯作者：
Sadda, SriniVas R.