Naska Sibel, Cenni Maria Cristina, Menna Elisabetta, Maffei Lamberto
Scuola Normale Superiore, piazza dei Cavalieri 7, 56100 Pisa, Italy.
Development. 2004 Aug;131(15):3559-70. doi: 10.1242/dev.01212. Epub 2004 Jun 23.
In the mammalian visual system, retinal ganglion cell (RGC) projections from each eye, initially intermixed within the dorsal-lateral geniculate nucleus (dLGN), become segregated during the early stages of development, occupying distinct eye-specific layers. Electrical activity has been suggested to play a role in this process; however, the cellular mechanisms underlying eye-specific segregation are not yet defined. It is known that electrical activity is among the strongest activators of the extracellular signal-regulated kinase (ERK) pathway. Moreover, the ERK pathway is involved in the plasticity of neural connections during development. We examine the role of ERK in the segregation of retinal afferents into eye-specific layers in the dLGN. The activation of this signaling cascade was selectively blocked along the retino-thalamic circuitry by specific inhibitors, and the distribution of RGC fibers in the dLGN was studied. Our results demonstrate that the blockade of ERK signaling prevents eye-specific segregation in the dLGN, providing evidence that ERK pathway is required for the proper development of retino-geniculate connections. Of particular interest is the finding that ERK mediates this process both at the retinal and geniculate level.
在哺乳动物视觉系统中，来自每只眼睛的视网膜神经节细胞（RGC）投射最初在背外侧膝状核（dLGN）内相互混合，在发育早期阶段开始分离，占据不同的眼特异性层。有研究表明电活动在此过程中发挥作用；然而，眼特异性分离背后的细胞机制尚未明确。已知电活动是细胞外信号调节激酶（ERK）通路最强的激活剂之一。此外，ERK通路参与发育过程中神经连接的可塑性。我们研究了ERK在视网膜传入纤维在dLGN中分离到眼特异性层过程中的作用。通过特异性抑制剂沿着视网膜 - 丘脑回路选择性阻断该信号级联的激活，并研究了RGC纤维在dLGN中的分布。我们的结果表明，ERK信号传导的阻断会阻止dLGN中的眼特异性分离，这证明ERK通路是视网膜 - 膝状体连接正常发育所必需的。特别有趣的是，发现ERK在视网膜和膝状体水平均介导这一过程。
