Iwai L, Kawasaki H
Department of Molecular and Systems Neurobiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Neuroscience. 2009 Apr 10;159(4):1326-37. doi: 10.1016/j.neuroscience.2009.02.010. Epub 2009 Feb 13.
When retinal waves are inhibited binocularly, eye-specific segregation of retinal axons is disrupted, and retinal axons from the two eyes remain intermingled in the lateral geniculate nucleus (LGN). This effect of binocular retinal wave inhibition is mediated by the lack of activity-dependent competition between retinal axons from the two eyes, but it is unknown whether this effect is also mediated by the developmental arrest of the LGN in an immature state. Here we find developmental markers of the LGN during eye-specific segregation. The expression levels of Purkinje cell protein 4 (PCP4/PEP19), transcription factor 7-like 2 (TCF7L2/TCF4) and LIM homeobox protein 9 (Lhx9) in the LGN change significantly during eye-specific segregation. Using PCP4, TCF7L2 and Lhx9 as developmental markers of the LGN, we examine whether LGN development is affected by binocular disruption of retinal waves during eye-specific segregation. Binocular injection of epibatidine strongly inhibits eye-specific segregation, whereas it does not affect the expression of PCP4, TCF7L2 and Lhx9. Furthermore, the expression of PCP4, TCF7L2 and Lhx9 is normal in binocularly enucleated animals and in mice treated with the monoamine oxidase A (MAOA) inhibitor, clorgyline. In addition, our experiments using LGN slice cultures show that the expression of PCP4 and TCF7L2 in LGN slices changes as in vivo. Our results suggest that LGN development proceeds, at least in part, even in the absence of retinal inputs. PCP4, TCF7L2 and Lhx9 should be useful to examine LGN development during eye-specific segregation in mice and in ferrets.
当双眼抑制视网膜波时，视网膜轴突的眼特异性分离会受到破坏，来自双眼的视网膜轴突会在外侧膝状体核（LGN）中保持混合状态。双眼视网膜波抑制的这种效应是由来自双眼的视网膜轴突之间缺乏活动依赖性竞争介导的，但尚不清楚这种效应是否也由LGN发育停滞在未成熟状态介导。在这里，我们发现了眼特异性分离过程中LGN的发育标志物。在眼特异性分离过程中，LGN中浦肯野细胞蛋白4（PCP4/PEP19）、转录因子7样2（TCF7L2/TCF4）和LIM同源盒蛋白9（Lhx9）的表达水平发生了显著变化。使用PCP4、TCF7L2和Lhx9作为LGN的发育标志物，我们研究了在眼特异性分离过程中，LGN的发育是否会受到视网膜波双眼破坏的影响。双眼注射埃博霉素强烈抑制眼特异性分离，而不影响PCP4、TCF7L2和Lhx9的表达。此外，在双眼摘除的动物和用单胺氧化酶A（MAOA）抑制剂氯吉兰治疗的小鼠中，PCP4、TCF7L2和Lhx9的表达是正常的。此外，我们使用LGN切片培养的实验表明，LGN切片中PCP4和TCF7L2的表达与体内情况一样发生变化。我们的结果表明，即使在没有视网膜输入的情况下，LGN的发育至少部分仍会进行。PCP4、TCF7L2和Lhx9应该有助于研究小鼠和雪貂在眼特异性分离过程中的LGN发育。
