Gdf6a is required for the initiation of dorsal-ventral retinal patterning and lens development
Gdf6a is required for the initiation of dorsal-ventral retinal patterning and lens development
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DOI：
10.1016/j.ydbio.2009.06.018
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发表时间：
2009-09-01
影响因子：
2.7
通讯作者：
Waskiewicz, Andrew J.
中科院分区：
文献类型：
--
作者：
French, Curtis R.;Erickson, Timothy;Waskiewicz, Andrew J.
脊椎动物视网膜的背腹模式对于视网膜神经节细胞（RGC）轴突到视觉处理中心的精确地形测绘至关重要。骨形态发生蛋白 (Bmp) 生长因子在脊椎动物模型中调节背侧视网膜特性，但这种信号传导的发育时间以及单个 Bmp 的相对作用仍不清楚。在本研究中，我们研究了两种斑马鱼 Bmp（Gdf6a 和 Bmp4）在背侧视网膜身份启动过程中以及随后晶状体分化过程中的功能。斑马鱼 Gdf6a 的敲低会阻止视网膜 Smad 磷酸化和背侧标记表达的启动，而 Bmp4 的敲低不会产生可辨别的视网膜表型。这些数据与异位表达 Bmp 的胚胎分析相结合，证明 Gdf6a 对于背侧视网膜身份的启动是必要且充分的。我们注意到 gdf6a 变形体中腹侧视网膜特性的显着扩展，证明背侧 BMP 信号传导拮抗腹侧标记物表达。最后，我们证明了 Gdf6a 在非神经眼组织中的作用。 Gdf6a 的敲低会导致晶状体特异性基因表达缺陷，并且当与 Bmp 信号抑制剂结合使用时，会破坏晶状体纤维细胞的分化。总而言之，这些数据表明 Gdf6a 独立于 Bmp4 启动背侧视网膜图案，并调节晶状体分化。 (C) 2009 Elsevier Inc. 保留所有权利。
Dorsal-ventral patterning of the vertebrate retina is essential for accurate topographic mapping of retinal ganglion cell (RGC) axons to visual processing centers. Bone morphogenetic protein (Bmp) growth factors regulate dorsal retinal identity in vertebrate models, but the developmental timing of this signaling and the relative roles of individual Bmps remain unclear. In this study, we investigate the functions of two zebrafish Bmps, Gdf6a and Bmp4, during initiation of dorsal retinal identity, and subsequently during lens differentiation. Knockdown of zebrafish Gdf6a blocks initiation of retinal Smad phosphorylation and dorsal marker expression, while knockdown of Bmp4 produces no discernable retinal phenotype. These data, combined with analyses of embryos ectopically expressing Bmps, demonstrate that Gdf6a is necessary and sufficient for initiation of dorsal retinal identity. We note a profound expansion of ventral retinal identity in gdf6a morphants, demonstrating that dorsal BMP signaling antagonizes ventral marker expression. Finally, we demonstrate a role for Gdf6a in non-neural ocular tissues. Knockdown of Gdf6a leads to defects in lens specific gene expression, and when combined with Bmp signaling inhibitors, disrupts lens fiber cell differentiation. Taken together, these data indicate that Gdf6a initiates dorsal retinal patterning independent of Bmp4, and regulates lens differentiation. (C) 2009 Elsevier Inc. All rights reserved.