Homophilic Dscam interactions control complex dendrite morphogenesis
Homophilic Dscam interactions control complex dendrite morphogenesis
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DOI：
10.1016/j.neuron.2007.04.013
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发表时间：
2007-05-03
期刊：
影响因子：
16.2
通讯作者：
Schmucker, Dietmar
中科院分区：
文献类型：
--
作者：
Hughes, Michael E.;Bortnick, Rachel;Schmucker, Dietmar
果蝇基因Dscam的选择性剪接导致多达38，016种不同的受体亚型，这些亚型通过亚型特异性嗜同性结合相互作用。我们报告说，Dscam控制细胞内在方面的树突指导在所有四个类别的树突树枝化（DA）神经元。单个神经元中Dscam的丢失导致自交的强烈增加。限制相邻的III类神经元的树突领域出现完整的突变神经元，这表明树突的自我回避，而不是heteroneuronal平铺，可能取决于Dscam。相同的Dscam亚型在两个DA神经元与重叠的树突领域的过度表达迫使空间隔离的两个领域，支持的模型，即DA神经元的树突分支使用亚型特异性的嗜同性相互作用，以确保最小的重叠。因此，Dscam的高度多样性的胞外结构域的嗜同性结合可能将相同的“核心”排斥机制的使用限制于细胞内在相互作用，而不干扰异神经元相互作用。
Alternative splicing of the Drosophila gene Dscam results in up to 38,016 different receptor isoforms proposed to interact by isoform-specific homophilic binding. We report that Dscam controls cell-intrinsic aspects of dendrite guidance in all four classes of dendrite arborization (da) neurons. Loss of Dscam in single neurons causes a strong increase in self-crossing. Restriction of dendritic fields of neighboring class III neurons appeared intact in mutant neurons, suggesting that dendritic self-avoidance, but not heteroneuronal tiling, may depend on Dscam. Overexpression of the same Dscam isoforms in two da neurons with overlapping dendritic fields forced a spatial segregation of the two fields, supporting the model that dendritic branches of da neurons use isoform-specific homophilic interactions to ensure minimal overlap. Homophilic binding of the highly diverse extracellular domains of Dscam may therefore limit the use of the same "core" repulsion mechanism to cell-intrinsic interactions without interfering with heteroneuronal interactions.