GABAergic synapses in C. elegans
S.C.P., J.D.W., J.E.R., and D.M.M. designed research; S.C.P., J.D.W., and J.E.R. performed research; M.S. and W.W.W. contributed unpublished reagents/analytic tools; S.C.P., J.D.W., J.E.R., and D.M.M. analyzed data; S.C.P. and D.M.M. wrote the paper.
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.
- Received June 22, 2011.
- Revision received August 16, 2011.
- Accepted September 6, 2011.