Research article
A genome-wide analysis reveals that the Drosophila transcription factor Lola promotes axon growth in part by suppressing expression of the actin nucleation factor Spire
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* Corresponding author: Edward Giniger ginigere@ninds.nih.gov
- † Equal contributors
1 Basic Neuroscience Program, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
2 National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892 USA
3 Fred Hutchinson Cancer Research Center, Seattle, WA, 98109 USA
4 Graduate Program in Molecular and Cellular Biology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, 98109 USA
Neural Development 2011, 6:37 doi:10.1186/1749-8104-6-37
Published: 30 November 2011Abstract
Background
The phylogenetically conserved transcription factor Lola is essential for many aspects of axon growth and guidance, synapse formation and neural circuit development in Drosophila. To date it has been difficult, however, to obtain an overall view of Lola functions and mechanisms.
Results
We use expression microarrays to identify the lola-dependent transcriptome in the Drosophila embryo. We find that lola regulates the expression of a large selection of genes that are known to affect each of several lola-dependent developmental processes. Among other loci, we find lola to be a negative regulator of spire, an actin nucleation factor that has been studied for its essential role in oogenesis. We show that spire is expressed in the nervous system and is required for a known lola-dependent axon guidance decision, growth of ISNb motor axons. We further show that reducing spire gene dosage suppresses this aspect of the lola phenotype, verifying that derepression of spire is an important contributor to the axon stalling phenotype of embryonic motor axons in lola mutants.
Conclusions
These data shed new light on the molecular mechanisms of many lola-dependent processes, and also identify several developmental processes not previously linked to lola 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 in vivo 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.