Petros Timothy J, Shrestha Brikha R, Mason Carol
Departments of Neuroscience, Pathology and Cell Biology, and Ophthalmology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
J Neurosci. 2009 Mar 18;29(11):3463-74. doi: 10.1523/JNEUROSCI.5655-08.2009.
At the optic chiasm, retinal ganglion cell (RGC) axons make the decision to either avoid or traverse the midline, a maneuver that establishes the binocular pathways. In mice, the ipsilateral retinal projection arises from RGCs in the peripheral ventrotemporal (VT) crescent of the retina. These RGCs express the guidance receptor EphB1, which interacts with ephrin-B2 on radial glia cells at the optic chiasm to repulse VT axons away from the midline and into the ipsilateral optic tract. However, because VT RGCs express more than one EphB receptor, the sufficiency and specificity of the EphB1 receptor in directing the ipsilateral projection is unclear. In this study, we use in utero retinal electroporation to demonstrate that ectopic EphB1 expression can redirect RGCs with a normally crossed projection to an ipsilateral trajectory. Moreover, EphB1 is specifically required for rerouting RGC projections ipsilaterally, because introduction of the highly similar EphB2 receptor is much less efficient in redirecting RGC fibers, even when expressed at higher surface levels. Introduction of EphB1-EphB2 chimeric receptors into RGCs reveals that both extracellular and juxtamembrane domains of EphB1 are required to efficiently convert RGC projections ipsilaterally. Together, these data describe for the first time functional differences between two highly similar Eph receptors at a decision point in vivo, with EphB1 displaying unique properties that efficiently drives the uncrossed retinal projection.
在视交叉处，视网膜神经节细胞（RGC）轴突决定是避开还是穿过中线，这一行为建立了双眼视觉通路。在小鼠中，同侧视网膜投射起源于视网膜周边颞下（VT）新月区的RGC。这些RGC表达导向受体EphB1，其与视交叉处放射状胶质细胞上的ephrin - B2相互作用，将VT轴突从中线排斥开，使其进入同侧视束。然而，由于VT RGC表达不止一种EphB受体，EphB1受体在引导同侧投射中的充分性和特异性尚不清楚。在本研究中，我们利用子宫内视网膜电穿孔技术证明，异位表达的EphB1可将正常交叉投射的RGC重定向至同侧轨迹。此外，EphB1是RGC投射同侧重定向所特需的，因为引入高度相似的EphB2受体在重定向RGC纤维方面效率低得多，即使其以更高的表面水平表达。将EphB1 - EphB2嵌合受体引入RGC表明，EphB1的细胞外结构域和近膜结构域对于有效地将RGC投射同侧化都是必需的。这些数据共同首次描述了在体内一个决策点上两种高度相似的Eph受体之间的功能差异，其中EphB1表现出能有效驱动未交叉视网膜投射的独特特性。
