RESUMEN
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.
Asunto(s)
Empalme Alternativo/fisiología , Axones/metabolismo , Proteínas de Drosophila/biosíntesis , Factores de Transcripción/biosíntesis , Secuencia de Aminoácidos/fisiología , Animales , Proteínas de Drosophila/genética , Drosophila melanogaster , Regulación de la Expresión Génica/fisiología , Datos de Secuencia Molecular , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , ARN/biosíntesis , ARN/genética , Homología de Secuencia de Aminoácido , Factores de Transcripción/genéticaRESUMEN
The pattern and level of expression of axon guidance proteins must be choreographed with exquisite precision for the nervous system to develop its proper connectivity. Previous work has shown that the transcription factor Lola is required for central nervous system (CNS) axons of Drosophila to extend longitudinally. We show here that Lola is simultaneously required to repel these same longitudinal axons away from the midline, and that it acts, in part, by augmenting the expression both of the midline repellant, Slit, and of its axonal receptor, Robo. Lola is thus the examplar of a class of axon guidance molecules that control axon patterning by coordinating the regulation of multiple, independent guidance genes, ensuring that they are co-expressed at the correct time, place and relative level.