Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Neuron. 2010 Feb 25;65(4):503-15. doi: 10.1016/j.neuron.2010.01.035.
Emerging evidence suggests that immune proteins regulate activity-dependent synapse formation in the central nervous system (CNS). Mice with mutations in class I major histocompatibility complex (MHCI) genes have incomplete eye-specific segregation of retinal ganglion cell (RGC) axon projections to the CNS. This effect has been attributed to causes that are nonretinal in origin. We show that a key component of MHCI receptor, CD3zeta, is expressed in RGCs. CD3zeta-deficient mice have reduced RGC dendritic motility, an increase in RGC dendritic density, and a selective defect of glutamate-receptor-mediated synaptic activity in the retina. Disrupted RGC synaptic activity and dendritic motility is associated with a failure of eye-specific segregation of RGC axon projections to the CNS. These results provide direct evidence of an unrecognized requirement for immune proteins in the developmental regulation of RGC synaptic wiring and indicate a possible retinal origin for the disruption of eye-specific segregation found in immune-deficient mice.
新兴证据表明，免疫蛋白调节中枢神经系统（CNS）中活性依赖的突触形成。在 I 类主要组织相容性复合体（MHCI）基因突变的小鼠中，视网膜神经节细胞（RGC）轴突投射到 CNS 的眼特异性分离不完全。这种效应归因于非视网膜起源的原因。我们表明，MHCI 受体的关键组成部分 CD3zeta 在 RGC 中表达。CD3zeta 缺陷型小鼠的 RGC 树突状运动减少，RGC 树突状密度增加，以及视网膜中谷氨酸受体介导的突触活动选择性缺陷。RGC 突触活动和树突状运动的中断与 RGC 轴突投射到 CNS 的眼特异性分离失败有关。这些结果为免疫蛋白在 RGC 突触连接的发育调节中未被识别的需求提供了直接证据，并表明免疫缺陷小鼠中发现的眼特异性分离中断可能具有视网膜起源。
