Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
Neural Dev. 2010 Nov 2;5:29. doi: 10.1186/1749-8104-5-29.
Many neurons in the central nervous system, including retinal ganglion cells (RGCs), possess asymmetric dendritic arbors oriented toward their presynaptic partners. How such dendritic arbors become biased during development in vivo is not well understood. Dendritic arbors may become oriented by directed outgrowth or by reorganization of an initially unbiased arbor. To distinguish between these possibilities, we imaged the dynamic behavior of zebrafish RGC dendrites during development in vivo. We then addressed how cell positioning within the retina, altered in heart-and-soul (has) mutants, affects RGC dendritic orientation.
In vivo multiphoton time-lapse analysis revealed that RGC dendrites initially exhibit exploratory behavior in multiple directions but progressively become apically oriented. The lifetimes of basal and apical dendrites were generally comparable before and during the period when arbors became biased. However, with maturation, the addition and extension rates of basal dendrites were slower than those of the apical dendrites. Oriented dendritic arbors were also found in misplaced RGCs of the has retina but there was no preferred orientation amongst the population. However, has RGCs always projected dendrites toward nearby neuropil where amacrine and bipolar cell neurites also terminated. Chimera analysis showed that the abnormal dendritic organization of RGCs in the mutant was non-cell autonomous.
Our observations show that RGC dendritic arbors acquire an apical orientation by selective and gradual restriction of dendrite addition to the apical side of the cell body, rather than by preferential dendrite stabilization or elimination. A biased arbor emerges at a stage when many of the dendritic processes still appear exploratory. The generation of an oriented RGC dendritic arbor is likely to be determined by cell-extrinsic cues. Such cues are unlikely to be localized to the basal lamina of the inner retina, but rather may be provided by cells presynaptic to the RGCs.
中枢神经系统中的许多神经元，包括视网膜神经节细胞（RGCs），具有朝向其突触前伙伴的不对称树突分支。在体内发育过程中，这些树突分支如何变得偏向尚不清楚。树突分支可能通过定向生长或最初无偏树突的重组来定向。为了区分这些可能性，我们在体内成像了斑马鱼 RGC 树突在发育过程中的动态行为。然后，我们研究了视网膜内细胞定位的变化如何影响 RGC 树突的方向，这种变化在心脏与灵魂（has）突变体中发生。
体内多光子延时分析显示，RGC 树突最初表现出多方向的探索行为，但逐渐变得向顶端定向。在树突变得偏向之前和期间，基底和顶端树突的寿命通常相似。然而，随着成熟，基底树突的添加和延伸速度比顶端树突慢。在 has 视网膜中错位的 RGC 中也发现了定向树突，但在群体中没有优先方向。然而，has RGC 总是将树突投射到附近的神经胶质中，那里也终止了无长突细胞和双极细胞的轴突。嵌合体分析表明，突变体中 RGC 的异常树突组织是非细胞自主的。
我们的观察表明，RGC 树突通过选择性和逐渐限制树突向细胞体顶端的添加来获得顶端取向，而不是通过优先稳定或消除树突。在许多树突过程仍然表现出探索性的阶段，出现了偏向的树突。有向 RGC 树突的产生可能取决于细胞外的线索。这些线索不太可能局限于内视网膜的基底层，而可能是由 RGC 突触前的细胞提供的。
