Abstract
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.
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Acknowledgements
We thank all the members of our lab for advice and assistance during the course of these experiments, and we thank C. Doe for helping us with the interpretation of vNR expression patterns, J. Lengyel for suggesting the comparison to mosquito, and H. Malik for discussion about the phylogenetic analysis. For comments on the manuscript, we thank S. Parkhurst, S. Tapscott, L. Buck and S. Henikoff. This work was supported by National Science Foundation grant IBN-9904519 (E.G.) and by a Grant-in-Aid for Scientific Research on Priority Areas (C) “Genome Science” from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#12202002 to T.A.).
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Goeke, S., Greene, E., Grant, P. et al. Alternative splicing of lola generates 19 transcription factors controlling axon guidance in Drosophila. Nat Neurosci 6, 917–924 (2003). https://doi.org/10.1038/nn1105
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DOI: https://doi.org/10.1038/nn1105
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