Goeke Scott, Greene Elizabeth A, Grant Paul K, Gates Michael A, Crowner Daniel, Aigaki Toshiro, Giniger Edward
Division of Basic Sciences and Program in Developmental Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024, USA.
Nat Neurosci. 2003 Sep;6(9):917-24. doi: 10.1038/nn1105.
The Drosophila melanogaster transcription factor Lola (longitudinals lacking) is a pivotal regulator of neural wiring that sets the precise expression levels of proteins that execute specific axon guidance decisions. Lola has a zinc finger DNA binding domain and a BTB (for Broad-complex, Tramtrack and Bric a brac) dimerization motif. We now show that alternative splicing of the lola gene creates a family of 19 transcription factors. All lola isoforms share a common dimerization domain, but 17 have their own unique DNA-binding domains. Seven of these 17 isoforms are present in the distantly-related Dipteran Anopheles gambiae, suggesting that the properties of specific isoforms are likely to be critical to lola function. Analysis of the expression patterns of individual splice variants and of the phenotypes of mutants lacking single isoforms supports this idea and establishes that the alternative forms of lola are responsible for different functions of this gene. Thus, in this system, the alternative splicing of a key transcription factor helps to explain how a small genome encodes all the information that is necessary to specify the enormous diversity of axonal trajectories.
果蝇的转录因子Lola（纵向缺失）是神经布线的关键调节因子，它能设定执行特定轴突导向决策的蛋白质的精确表达水平。Lola具有一个锌指DNA结合结构域和一个BTB（即Broad-complex、Tramtrack和Bric a brac）二聚化基序。我们现在表明，lola基因的可变剪接产生了一个由19种转录因子组成的家族。所有Lola异构体都共享一个共同的二聚化结构域，但其中17种具有各自独特的DNA结合结构域。这17种异构体中的7种存在于远缘双翅目冈比亚按蚊中，这表明特定异构体的特性可能对Lola的功能至关重要。对单个剪接变体的表达模式以及缺乏单个异构体的突变体表型的分析支持了这一观点，并确定lola的不同形式负责该基因的不同功能。因此，在这个系统中，关键转录因子的可变剪接有助于解释一个小基因组如何编码指定轴突轨迹的巨大多样性所需的所有信息。
