PT - JOURNAL ARTICLE AU - Sarah C. Petersen AU - Joseph D. Watson AU - Janet E. Richmond AU - Mihail Sarov AU - Walter W. Walthall AU - David M. Miller III TI - A Transcriptional Program Promotes Remodeling of GABAergic Synapses in <em>Caenorhabditis elegans</em> AID - 10.1523/JNEUROSCI.3181-11.2011 DP - 2011 Oct 26 TA - The Journal of Neuroscience PG - 15362--15375 VI - 31 IP - 43 4099 - http://www.jneurosci.org/content/31/43/15362.short 4100 - http://www.jneurosci.org/content/31/43/15362.full SO - J. Neurosci.2011 Oct 26; 31 AB - 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.