Expression of SPIG1 Reveals Development of a Retinal Ganglion Cell Subtype Projecting to the Medial Terminal Nucleus in the Mouse
Expression of SPIG1 Reveals Development of a Retinal Ganglion Cell Subtype Projecting to the Medial Terminal Nucleus in the Mouse
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DOI：
10.1371/journal.pone.0001533
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发表时间：
2008-02-06
期刊：
影响因子：
3.7
通讯作者：
Noda, Masaharu
中科院分区：
文献类型：
--
作者：
Yonehara, Keisuke;Shintani, Takafumi;Noda, Masaharu
视觉信息通过大约十几种不同类型的视网膜神经节细胞（RGC）传递到大脑，这些细胞由特征性的形态学、生理学和中央投射定义。然而，我们对这些平行途径如何发展的理解仍处于起步阶段，因为很少有对应于单个RGC类型的分子标记可用。以前，我们报道了一种分泌蛋白，SPIG 1（克隆名称; D/Bsp 120 I #1），优先在发育中的鸡视网膜的背侧区域表达。在这里，我们产生了敲入小鼠，用绿色荧光蛋白可视化SPIG 1表达细胞。我们发现，小鼠视网膜被细分为两个不同的域SPIG 1的表达和SPIG 1有效地标志着一个独特的亚型的视网膜神经节细胞在新生儿时期。SPIG 1阳性RGCs在背颞区投射到背外侧膝状体核（dLGN）、上级丘和辅助视系统（AOS）。相比之下，在剩余的区域，这里命名为泛腹鼻域，SPIG 1阳性细胞形成一个规则的马赛克和项目专门的中间终核（MTN）的AOS介导的视动性眼球震颤早在P1。早在P3，它们的树突就与内网状层的胆碱能无长突层共层。这些结果表明，这些SPIG 1阳性细胞是ON方向选择性神经节细胞（DSGCs）。此外，MTN投射细胞在泛腹鼻域显然是由两个不同的，但相互依存的规则马赛克取决于SPIG 1的存在或不存在，表明它们包括两个功能不同的亚型的ON DSGCs。规则马赛克的形成似乎开始于产前阶段结束时，并在P6的细胞死亡高峰期完成。SPIG 1将为进一步研究ON DSGCs的发育和功能提供一个有用的分子标记。
Visual information is transmitted to the brain by roughly a dozen distinct types of retinal ganglion cells (RGCs) defined by a characteristic morphology, physiology, and central projections. However, our understanding about how these parallel pathways develop is still in its infancy, because few molecular markers corresponding to individual RGC types are available. Previously, we reported a secretory protein, SPIG1(clone name; D/Bsp120I #1), preferentially expressed in the dorsal region in the developing chick retina. Here, we generated knock-in mice to visualize SPIG1-expressing cells with green fluorescent protein. We found that the mouse retina is subdivided into two distinct domains for SPIG1 expression and SPIG1 effectively marks a unique subtype of the retinal ganglion cells during the neonatal period. SPIG1-positive RGCs in the dorsotemporal domain project to the dorsal lateral geniculate nucleus (dLGN), superior colliculus, and accessory optic system (AOS). In contrast, in the remaining region, here named the pan-ventronasal domain, SPIG1-positive cells form a regular mosaic and project exclusively to the medial terminal nucleus (MTN) of the AOS that mediates the optokinetic nystagmus as early as P1. Their dendrites costratify with ON cholinergic amacrine strata in the inner plexiform layer as early as P3. These findings suggest that these SPIG1-positive cells are the ON direction selective ganglion cells (DSGCs). Moreover, the MTN-projecting cells in the pan-ventronasal domain are apparently composed of two distinct but interdependent regular mosaics depending on the presence or absence of SPIG1, indicating that they comprise two functionally distinct subtypes of the ON DSGCs. The formation of the regular mosaic appears to be commenced at the end of the prenatal stage and completed through the peak period of the cell death at P6. SPIG1 will thus serve as a useful molecular marker for future studies on the development and function of ON DSGCs.