Program in Neuroscience, Department of Neurobiology and Anatomy, and Brain Institute, University of Utah Medical Center, Salt Lake City, UT 84132, USA.
Dev Biol. 2010 Aug 15;344(2):784-94. doi: 10.1016/j.ydbio.2010.05.512. Epub 2010 Jun 9.
In the zebrafish retinotectal system, retinal ganglion cells (RGCs) project topographically along anterior-posterior (A-P) and dorsal-ventral (D-V) axes to innervate their primary target, the optic tectum. In the nevermind (nev) mutant, D-V positional information is not maintained by dorsonasal retinal axons as they project through the optic tract to the tectum. Here we present a detailed phenotypic analysis of the retinotectal projection in nev and show that dorsonasal axons do eventually find their correct location on the tectum, albeit after taking a circuitous path. Interestingly, nev seems to be specifically required for retinal axons but not for several non-retinal axon tracts. In addition, we find that nev is required both cell autonomously and cell nonautonomously for proper lamination of the retina. We show that nev encodes Cyfip2 (Cytoplasmic FMRP interacting protein 2) and is thus the first known mutation in a vertebrate Cyfip family member. Finally, we show that CYFIP2 acts cell autonomously in the D-V sorting of dorsonasal RGC axons in the optic tract. CYFIP2 is a highly conserved protein that lacks known domains or structural motifs but has been shown to interact with Rac and the fragile-X mental retardation protein, suggesting intriguing links to cytoskeletal dynamics and RNA regulation.
在斑马鱼的视网膜-视顶盖系统中，视网膜神经节细胞（RGCs）沿前后（A-P）和背腹（D-V）轴进行拓扑投射，以将其初级靶标——视顶盖神经纤维支配。在 nev 突变体中，背侧-鼻侧视网膜轴突在穿过视束投射到视顶盖时，不会维持 D-V 位置信息。在这里，我们对 nev 中的视网膜-视顶盖投射进行了详细的表型分析，结果表明背侧-鼻侧轴突最终确实找到了它们在视顶盖的确切位置，尽管它们走了一条迂回的路径。有趣的是，nev 似乎专门用于视网膜轴突，但对几个非视网膜轴突束没有作用。此外，我们发现 nev 对视网膜的正确分层既需要细胞自主性，也需要细胞非自主性。我们表明 nev 编码 Cyfip2（细胞质 FMRP 相互作用蛋白 2），因此是第一个在脊椎动物 Cyfip 家族成员中发现的突变。最后，我们表明 CYFIP2 在视束中背侧-鼻侧 RGC 轴突的 D-V 分拣中具有细胞自主性。CYFIP2 是一种高度保守的蛋白质，缺乏已知的结构域或结构基序，但已被证明与 Rac 和脆性 X 智力迟钝蛋白相互作用，这表明与细胞骨架动力学和 RNA 调控有有趣的联系。
