Journal
JOURNAL OF NEUROSCIENCE
Volume 31, Issue 43, Pages 15362-15375Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3181-11.2011
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Funding
- National Institutes of Health (NIH) [R21 MH077302, R01 NS26115, T32 GM08554, F31 NS063669, F31 NS049743, R01 MH073156]
- NIH National Center for Research Resources
- Japanese National BioResource Project
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Although transcription factors are known to regulate synaptic plasticity, downstream genes that contribute to neural circuit remodeling are largely undefined. In Caenorhabditis elegans, GABAergic Dorsal D (DD) motor neuron synapses are relocated to new sites during larval development. This remodeling program is blocked in Ventral D (VD) GABAergic motor neurons by the COUP-TF (chicken ovalbumin upstream promoter transcription factor) homolog, UNC-55. We exploited this UNC-55 function to identify downstream synaptic remodeling genes that encode a diverse array of protein types including ion channels, cytoskeletal components, and transcription factors. We show that one of these targets, the Iroquois-like homeodomain protein, IRX-1, functions as a key regulator of remodeling in DD neurons. Our discovery of irx-1 as an unc-55-regulated target defines a transcriptional pathway that orchestrates an intricate synaptic remodeling program. Moreover, the well established roles of these conserved transcription factors in mammalian neural development suggest that a similar cascade may also control synaptic plasticity in more complex nervous systems.
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