Kay Jeremy N, Roeser Tobias, Mumm Jeff S, Godinho Leanne, Mrejeru Ana, Wong Rachel O L, Baier Herwig
Program in Neuroscience and Department of Physiology, University of California, San Francisco, 513 Parnassus Avenue Box 0444, San Francisco, CA 94143, USA.
Development. 2004 Mar;131(6):1331-42. doi: 10.1242/dev.01040. Epub 2004 Feb 18.
The inner plexiform layer (IPL) of the vertebrate retina comprises functionally specialized sublaminae, representing connections between bipolar, amacrine and ganglion cells with distinct visual functions. Developmental mechanisms that target neurites to the correct synaptic sublaminae are largely unknown. Using transgenic zebrafish expressing GFP in subsets of amacrine cells, we imaged IPL formation and sublamination in vivo and asked whether the major postsynaptic cells in this circuit, the ganglion cells, organize the presynaptic inputs. We found that in the lak/ath5 mutant retina, where ganglion cells are never born, formation of the IPL is delayed, with initial neurite outgrowth ectopically located and grossly disorganized. Over time, the majority of early neurite projection errors are corrected, and major ON and OFF sublaminae do form. However, focal regions of disarray persist where sublaminae do not form properly. Bipolar axons, which arrive later, are targeted correctly, except at places where amacrine stratification is disrupted. The lak mutant phenotype reveals that ganglion cells have a transient role organizing the earliest amacrine projections to the IPL. However, it also suggests that amacrine cells interact with each other during IPL formation; these interactions alone appear sufficient to form the IPL. Furthermore, our results suggest that amacrines may guide IPL sublamination by providing stratification cues for other cell types.
脊椎动物视网膜的内网层（IPL）由功能特化的亚层组成，代表具有不同视觉功能的双极细胞、无长突细胞和神经节细胞之间的连接。将神经突靶向正确突触亚层的发育机制在很大程度上尚不清楚。利用在无长突细胞亚群中表达绿色荧光蛋白（GFP）的转基因斑马鱼，我们对体内IPL的形成和分层进行了成像，并探究了该回路中的主要突触后细胞——神经节细胞是否组织突触前输入。我们发现，在lak/ath5突变体视网膜中，神经节细胞从未生成，IPL的形成延迟，最初的神经突生长位置异常且严重紊乱。随着时间的推移，大多数早期神经突投射错误得到纠正，主要的ON和OFF亚层确实形成。然而，亚层未正确形成的紊乱局部区域仍然存在。稍后到达的双极轴突靶向正确，除了无长突细胞分层被破坏的地方。lak突变体表型表明，神经节细胞在组织最早的无长突细胞向IPL的投射中具有短暂作用。然而，这也表明无长突细胞在IPL形成过程中相互作用；仅这些相互作用似乎就足以形成IPL。此外，我们的结果表明，无长突细胞可能通过为其他细胞类型提供分层线索来引导IPL分层。
