A Transcriptional Program Promotes Remodeling of GABAergic Synapses inCaenorhabditis elegans

Autor: David M. Miller, Mihail Sarov, Walter W. Walthall, Sarah C. Petersen, Janet E. Richmond, Joseph D. Watson
Rok vydání: 2011
Předmět:
Zdroj: The Journal of Neuroscience. 31:15362-15375
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.3181-11.2011
Popis: Although transcription factors are known to regulate synaptic plasticity, downstream genes that contribute to neural circuit remodeling are largely undefined. InCaenorhabditis 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 ofirx-1as anunc-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.
Databáze: OpenAIRE