Synaptic and genomic responses to JNK and AP-1 signaling in <it>Drosophila </it>neurons

• Main Authors: Bohmann Dirk, Patel Chirag, Navratilova Zaneta, Narayanan Radhakrishnan, Etter Paul D, Jasper Heinrich, Ramaswami Mani
• Format: Article
• Language: English
• Published: BMC 2005-06-01
• Series: BMC Neuroscience
• Online Access: http://www.biomedcentral.com/1471-2202/6/39

<p>Abstract</p> <p>Background</p> <p>The transcription factor AP-1 positively controls synaptic plasticity at the <it>Drosophila </it>neuromuscular junction. Although in motor neurons, JNK has been shown to activate AP-1, a positive regulator of growth and strength at the larval NMJ, the consequences of JNK activation are poorly studied. In addition, the downstream transcriptional targets of JNK and AP-1 signaling in the <it>Drosophila </it>nervous system have yet to be identified. Here, we further investigated the role of JNK signaling at this model synapse employing an activated form of JNK-kinase; and using Serial Analysis of Gene Expression and oligonucleotide microarrays, searched for candidate early targets of JNK or AP-1 dependent transcription in neurons.</p> <p>Results</p> <p>Temporally-controlled JNK induction in postembryonic motor neurons triggers synaptic growth at the NMJ indicating a role in developmental plasticity rather than synaptogenesis. An unexpected observation that JNK activation also causes a reduction in transmitter release is inconsistent with JNK functioning solely through AP-1 and suggests an additional, yet-unidentified pathway for JNK signaling in motor neurons. SAGE profiling of mRNA expression helps define the neural transcriptome in <it>Drosophila</it>. Though many putative AP-1 and JNK target genes arose from the genomic screens, few were confirmed in subsequent validation experiments. One potentially important neuronal AP-1 target discovered, <it>CG6044</it>, was previously implicated in olfactory associative memory. In addition, 5 mRNAs regulated by RU486, a steroid used to trigger conditional gene expression were identified.</p> <p>Conclusion</p> <p>This study demonstrates a novel role for JNK signaling at the larval neuromuscular junction and provides a quantitative profile of gene transcription in <it>Drosophila </it>neurons. While identifying potential JNK/AP-1 targets it reveals the limitations of genome-wide analyses using complex tissues like the whole brain.</p>