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A transcriptional program promotes remodeling of GABAergic synapses in Caenorhabditis elegans

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Sarov,  Mihail
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Zitation

Petersen, S. C., Watson, J. D., Richmond, J. E., Sarov, M., Walthall, W. W., & Miller, D. M. (2011). A transcriptional program promotes remodeling of GABAergic synapses in Caenorhabditis elegans. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience, 31(43), 15362-15375.


Zitierlink: https://hdl.handle.net/21.11116/0000-0001-09D1-9
Zusammenfassung
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.