Abstract
BackgroundFormation of synaptic connections is a dynamic and highly regulated process. Little is known about the gene networks that regulate synaptic growth and how they balance stimulatory and restrictive signals.ResultsHere we show that the neuronally expressed transcription factor gene erect wing (ewg) is a major target of the RNA binding protein ELAV and that EWG restricts synaptic growth at neuromuscular junctions. Using a functional genomics approach we demonstrate that EWG acts primarily through increasing mRNA levels of genes involved in transcriptional and post-transcriptional regulation of gene expression, while genes at the end of the regulatory expression hierarchy (effector genes) represent only a minor portion, indicating an extensive regulatory network. Among EWG-regulated genes are components of Wingless and Notch signaling pathways. In a clonal analysis we demonstrate that EWG genetically interacts with Wingless and Notch, and also with TGF-β and AP-1 pathways in the regulation of synaptic growth.ConclusionOur results show that EWG restricts synaptic growth by integrating multiple cellular signaling pathways into an extensive regulatory gene expression network.
Highlights
Formation of synaptic connections is a dynamic and highly regulated process
FLP/FRT mediated recombination will result in loss of the ewg cDNA and lead to expression of GAL4 in neurons that can be visualized in the presence of a UAS-CD8::green fluorescent protein (GFP) transgene (Figure 1a,c,e-i) [17,24,25]
Overexpression of AP-1 [4] and mutants in regulatory genes involved in Wnt/Wingless and transforming growth factor (TGF)-β/bone morphogenetic protein (BMP) pathways [9,47,48,49] can increase bouton numbers, suggesting that synaptic growth is regulated through the balance of stimulatory and restrictive signals
Summary
Formation of synaptic connections is a dynamic and highly regulated process. Little is known about the gene networks that regulate synaptic growth and how they balance stimulatory and restrictive signals. Synaptic connections are formed during development and continue to be remodeled in the adult nervous system Such morphological changes are implicated as the cellular basis of neuronal information processing and storage in the brain [1]. Several signaling pathways with prominent roles in development have been shown to regulate synaptic growth These include Wnt/Wingless and transforming growth factor (TGF)-β/bone morphogenetic protein (BMP) signaling pathways (reviewed in [2,3]), as well as the jun kinase pathway [4]. All of these pathways stimulate synaptic growth at neuromuscular junctions (NMJs) in Drosophila larvae [5,6,7,8,9], a model system for synaptic plasticity of glutamergic synapses [10]. A major focus of these studies has been the Genome Biology 2008, 9:R73 http://genomebiology.com/2008/9/4/R73
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