Ellsworth Charlene A, Lyckman Alvin W, Feldheim David A, Flanagan John G, Sur Mriganka
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Comp Neurol. 2005 Jul 25;488(2):140-51. doi: 10.1002/cne.20602.
Sensory axons are targeted to modality-specific nuclei in the thalamus. Retinal ganglion cell axons project retinotopically to their principal thalamic target, the dorsal lateral geniculate nucleus (LGd), in a pattern likely dictated by the expression of molecular gradients in the LGd. Deafferenting the auditory thalamus induces retinal axons to innervate the medial geniculate nucleus (MGN). These retino-MGN projections also show retinotopic organization. Here we show that ephrin-A2 and -A5, which are expressed in similar gradients in the MGN and LGd, can be used to pattern novel retinal projections in the MGN. As in the LGd, retinal axons from each eye terminate in discrete eye-specific zones in the MGN of rewired wild-type and ephrin-A2/A5 knockout mice. However, ipsilateral eye axons, which arise from retinal regions of high EphA5 receptor expression and represent central visual field, terminate in markedly different ways in the two mice. In rewired wild-type mice, ipsilateral axons specifically avoid areas of high ephrin expression in the MGN. In rewired ephrin knockout mice, ipsilateral projections shift in location and spread more broadly, leading to an expanded representation of the ipsilateral eye in the MGN. Similarly, ipsilateral projections to the LGd in ephrin knockout mice are shifted and are more widespread than in the LGd of wild-type mice. In the MGN, as in the LGd, terminations from the two eyes show little overlap even in the knockout mice, suggesting that local interocular segregation occurs regardless of other patterning determinants. Our data demonstrate that graded topographic labels, such as the ephrins, can serve to shape multiple related aspects of afferent patterning, including topographic mapping and the extent and spread of eye-specific projections. Furthermore, when mapping labels and other cues are expressed in multiple target zones, novel projections are patterned according to rules that operate in their canonical targets.
感觉轴突靶向丘脑的模式特异性核团。视网膜神经节细胞轴突以视网膜拓扑方式投射到其主要丘脑靶区——背外侧膝状体核（LGd），这种模式可能由LGd中分子梯度的表达所决定。去除听觉丘脑的传入神经会诱导视网膜轴突支配内侧膝状体核（MGN）。这些视网膜 - MGN投射也呈现视网膜拓扑组织。在此我们表明，在MGN和LGd中以相似梯度表达的ephrin - A2和 - A5可用于在MGN中形成新的视网膜投射模式。与在LGd中一样，来自每只眼睛的视网膜轴突在重新布线的野生型和ephrin - A2/A5基因敲除小鼠的MGN中终止于离散的眼特异性区域。然而，来自高EphA5受体表达视网膜区域且代表中央视野的同侧眼轴突，在这两种小鼠中的终止方式明显不同。在重新布线的野生型小鼠中，同侧轴突特异性避开MGN中高ephrin表达区域。在重新布线的ephrin基因敲除小鼠中，同侧投射在位置上发生偏移且分布更广泛，导致MGN中同侧眼的代表区域扩大。同样，与野生型小鼠的LGd相比，ephrin基因敲除小鼠中到LGd的同侧投射也发生了偏移且更广泛。在MGN中，如同在LGd中一样，即使在基因敲除小鼠中，两只眼睛的投射终止也几乎没有重叠，这表明局部眼间分离的发生与其他模式决定因素无关。我们的数据表明，诸如ephrin这样的分级拓扑标记可用于塑造传入模式的多个相关方面包括拓扑映射以及眼特异性投射的范围和分布。此外，当映射标记和其他线索在多个靶区表达时，新的投射会根据在其经典靶区起作用的规则形成模式。
