A transcriptional program promotes remodeling of GABAergic synapses in Caenorhabditis elegans.
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.
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Sarah C
SC
Petersen
Joseph D
JD
Watson
Janet E
JE
Richmond
Mihail
M
Sarov
Walter W
WW
Walthall
David M
DM
Miller
D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D020869:Gene Expression Profiling / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis / Q000379:methods; D009046:Motor Neurons / Q000378:metabolism; D009068:Movement / Q000502:physiology; D009154:Mutation / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050987:Vesicle-Associated Membrane Protein 1 / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018079:Receptors, GABA; D014157:Transcription Factors; D050987:Vesicle-Associated Membrane Protein 1; D049452:Green Fluorescent Proteins; C077588:UNC-5 protein, C elegans; D005680:gamma-Aminobutyric Acid