A genome-wide analysis reveals that the <it>Drosophila </it>transcription factor Lola promotes axon growth in part by suppressing expression of the actin nucleation factor Spire

• Main Authors: Gates Michael A, Kannan Ramakrishnan, Giniger Edward
• Format: Article
• Language: English
• Published: BMC 2011-11-01
• Series: Neural Development
• Online Access: http://www.neuraldevelopment.com/content/6/1/37

<p>Abstract</p> <p>Background</p> <p>The phylogenetically conserved transcription factor Lola is essential for many aspects of axon growth and guidance, synapse formation and neural circuit development in <it>Drosophila</it>. To date it has been difficult, however, to obtain an overall view of Lola functions and mechanisms.</p> <p>Results</p> <p>We use expression microarrays to identify the <it>lola</it>-dependent transcriptome in the <it>Drosophila </it>embryo. We find that <it>lola </it>regulates the expression of a large selection of genes that are known to affect each of several <it>lola</it>-dependent developmental processes. Among other loci, we find <it>lola </it>to be a negative regulator of <it>spire</it>, an actin nucleation factor that has been studied for its essential role in oogenesis. We show that <it>spire </it>is expressed in the nervous system and is required for a known <it>lola</it>-dependent axon guidance decision, growth of ISNb motor axons. We further show that reducing <it>spire </it>gene dosage suppresses this aspect of the <it>lola </it>phenotype, verifying that derepression of <it>spire </it>is an important contributor to the axon stalling phenotype of embryonic motor axons in <it>lola </it>mutants.</p> <p>Conclusions</p> <p>These data shed new light on the molecular mechanisms of many <it>lola</it>-dependent processes, and also identify several developmental processes not previously linked to <it>lola </it>that are apt to be regulated by this transcription factor. These data further demonstrate that excessive expression of the actin nucleation factor Spire is as deleterious for axon growth <it>in vivo </it>as is the loss of Spire, thus highlighting the need for a balance in the elementary steps of actin dynamics to achieve effective neuronal morphogenesis.</p>