Nature Neuroscience6, 917 - 924 (2003)
Published online: 3 August 2003; | doi:10.1038/nn1105
Alternative splicing of lola generates 19 transcription factors controlling axon guidance in Drosophila
Scott Goeke1, Elizabeth A. Greene1, Paul K. Grant1, Michael A. Gates1, Daniel Crowner1, Toshiro Aigaki2, 3
& Edward Giniger1
1
Division of Basic Sciences and Program in Developmental Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024, USA.
2
Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
3
Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Osaka 565-0082, Japan.
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.
