A transcriptional program promotes remodeling of GABAergic synapses in Caenorhabditis elegans.

Petersen SC, Watson JD, Richmond JE, Sarov M, Walthall WW, Miller DM
J Neurosci. 2011 31 (43): 15362-75

PMID: 22031882 · PMCID: PMC3229156 · DOI:10.1523/JNEUROSCI.3181-11.2011

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.

MeSH Terms (23)

Analysis of Variance Animals Animals, Genetically Modified Caenorhabditis elegans Caenorhabditis elegans Proteins Embryo, Nonmammalian gamma-Aminobutyric Acid Gene Expression Profiling Green Fluorescent Proteins Homeodomain Proteins Microarray Analysis Motor Neurons Movement Mutation Receptors, Cell Surface Receptors, GABA RNA, Messenger RNA Interference Spinal Cord Synapses Time Factors Transcription Factors Vesicle-Associated Membrane Protein 1

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