Probabilistic splicing of Dscam1 establishes identity at the level of single neurons.
Probabilistic splicing of Dscam1 establishes identity at the level of single neurons.
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DOI：
10.1016/j.cell.2013.10.018
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发表时间：
2013-11-21
期刊：
影响因子：
64.5
通讯作者：
Zipursky SL
中科院分区：
文献类型：
--
作者：
Miura SK;Martins A;Zhang KX;Graveley BR;Zipursky SL
果蝇Dscam1基因通过选择性剪接编码大量的细胞识别分子。它们表现出同种型特异性的嗜同性结合，并调节自我回避，即来自同一细胞的神经突相互排斥的趋势。遗传实验表明，不同的细胞必须表达不同的同种型。这是如何实现的尚不清楚，因为替代外显子在体内的表达尚未显示。在这里，我们修改了内源性Dscam1基因座产生剪接报告外显子4的所有变体。我们证明，剪接不会发生在一个特定的细胞类型的方式，细胞识别其独特的位置表达不同的外显子4的变体在不同的动物，并在确定的神经元剪接可以随时间而变化。可能的表达是兼容的广泛作用，通过自我回避的神经回路组装，是不兼容的模型，其中特定的同种型Dscam 1介导的过程之间的识别不同的细胞。
The Drosophila Dscam1 gene encodes a vast number of cell recognition molecules through alternative splicing. These exhibit isoform-specific homophilic binding and regulate self-avoidance, the tendency of neurites from the same cell to repel one another. Genetic experiments indicate that different cells must express different isoforms. How this is achieved is not known, as the expression of alternative exons in vivo has not been shown. Here, we modified the endogenous Dscam1 locus to generate splicing reporters for all variants of exon 4. We demonstrate that splicing does not occur in a cell-type specific fashion, that cells identified by their unique locations express different exon 4 variants in different animals, and that splicing in identified neurons can change over time. Probabilistic expression is compatible with a widespread role in neural circuit assembly through self-avoidance and is incompatible with models in which specific isoforms of Dscam1 mediate recognition between processes of different cells.
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