Ocular and cerebellar defects in zebrafish induced by overexpression of the LIM domains of the islet-3 LIM/homeodomain protein
Ocular and cerebellar defects in zebrafish induced by overexpression of the LIM domains of the islet-3 LIM/homeodomain protein
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DOI：
10.1016/s0896-6273(00)81239-8
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发表时间：
1997-03-01
期刊：
影响因子：
16.2
通讯作者：
Okamoto, H
中科院分区：
文献类型：
--
作者：
Kikuchi, Y;Segawa, H;Okamoto, H
Islet-3是一种LIM/同源结构域蛋白，在斑马鱼（Danio rerio）胚胎中枢神经系统的眼和推定顶盖中特异性表达。蛋白质的过表达LIM（Isl-3）在胚胎中仅由Islet-3 LIM结构域组成，特异性地阻止视泡的形成，在受精后14小时和20小时之间引起中脑和后脑区域wnt 1、enrailed 2和pax 2表达的异常终止;并且在20小时和26小时之间该区域的形态发生运动严重受损，这通常应该导致小脑原基的形成。这些缺陷都是通过同时过表达胰岛3来挽救的，这表明LIM（Isl-3）充当胰岛3的特异性显性负性变体。这些数据，结合镶嵌分析的结果，表明，胰岛3被激活的推定的LIM结合辅因子和功能，以促进外翻的视泡和维持相互之间的相互作用中脑和中脑-后颅边界的正常发展所必需的这一地区。
Islet-3 is an LIM/homeodomain protein that is expressed specifically in the eyes and the presumptive tectum in the central nervous system of zebrafish (Danio rerio) embryos. Overexpression of the protein (LIM(Isl-3))consisting only of the Islet-3 LIM domains in embryos specifically prevented formation of the optic vesicles; caused abnormal termination of the expression of wnt1, engrailed2, and pax2 in the mesencephalic and metencephalic region between 14 hr and 20 hr postfertilization; and severely impaired morphogenetic movement in this region between 20 hr and 26 hr, which should normally lead to formation of the cerebellar primordium. Such defects were all rescued by simultaneous overexpression of Islet-3, suggesting that LIM(Isl-3) acted as a specific dominant-negative variant of Islet-3. These data, combined with the results of mosaic analyses, suggest that Islet-3 is activated by putative LIM-binding cofactors and functions to promote evagination of the optic vesicles and to maintain reciprocal interaction between the mesencephalon and the mesencephalic-metencephalic boundary essential for normal development of this region.