Drosophila eye developmental defect caused by elevation of the activity of the LIM-homeodomain protein, Lmx1a, requires its association with the Co-activator Chip
Drosophila eye developmental defect caused by elevation of the activity of the LIM-homeodomain protein, Lmx1a, requires its association with the Co-activator Chip
复制标题
LIM-同源域蛋白 Lmx1a 活性升高导致果蝇眼睛发育缺陷，需要将其与辅激活芯片结合起来
DOI：
10.1016/j.bbrc.2015.12.089
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发表时间：
2016
影响因子：
3.1
通讯作者：
Wu Shian
中科院分区：
文献类型：
--
作者：
Wang Ping;Chen Yan;Li Chaojie;Zhao Wunan;Wang Feng;Lin Xiaohui;Cao Lei;Li Shanshan;Hu Liangchang;Gao Yang;Li Yuanpei;Wu Shian
LIM-HD家族成员Lmx 1a已成功用于从其他细胞类型诱导多巴胺能神经元，因此在帕金森病的替代疗法中显示出重要意义，但其潜在机制仍然难以捉摸。在这项研究中，我们使用果蝇眼作为模型系统来研究dLmx 1a（人类Lmx 1a的果蝇同源物）的强制表达如何改变细胞识别。我们发现dLmx 1as的异位表达抑制果蝇眼组织的形成，并确定LIM和HD是两个重要的结构域。dLmx 1a需要并物理结合到Chip，一种众所周知的LIM-HD蛋白的辅因子。芯片连接两个dLmx 1a蛋白质形成功能性四聚体复合物。此外，我们提供的证据表明，dLmx 1a表达的结果抑制两个视网膜决定基因的眼睛缺席（EYA）和字符串（STG）。综上所述，我们的研究结果确定Chip作为dLmx 1a的新伴侣，通过抑制eya和stg表达来改变果蝇眼细胞的分化，并为进一步了解Lmx 1a决定细胞命运的分子机制提供了动物模型。
The LIM-homeodomain (LIM-HD) family member Lmx1a has been successfully used to induce dopaminergic neurons from other cell types, thus showing significant implications in replacement therapies of Parkinson's disease, but the underlying mechanism remains elusive. In this study, we usedDrosophilaeye as a model system to investigate how forced expression ofdLmx1a, the fly homolog of humanLmx1a, alters cell identify. We found that ectopic expression ofdLmx1asuppresses the formation ofDrosophilaeye tissue and identified the LIM and HD as two essential domains. dLmx1a requires and physically binds to Chip, a well-known cofactor of LIM-HD proteins. Chip connects two dLmx1a proteins to form a functional tetrameric complex. In addition, we provide evidence showing thatdLmx1aexpression results in the suppression of two retina determination geneeyes absent(eya) andstring(stg). Taken together, our findings identified Chip as a novel partner of dLmx1a to alter cell differentiation inDrosophilaeye through repressingeyaandstgexpression, and provide an animal model for further understanding the molecular mechanism whereby Lmx1a determines cell fate.