Dataset Information

UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways.

ABSTRACT: The UNC-5 receptor mediates axon repulsion from UNC-6/netrin through UNC-40 dependent (UNC-5 + UNC-40) and independent (UNC-5 alone) signaling pathways. It has been shown that UNC-40-dependent signaling is required for long-range repulsion of UNC-6/netrin; however, the mechanisms used to regulate distinct UNC-5 signaling pathways are poorly understood. We found that the C. elegans transforming growth factor beta (TGF-beta) family ligand UNC-129, graded opposite to UNC-6/netrin, functions independent of the canonical TGF-beta receptors to regulate UNC-5 cellular responses. Our observations indicates that UNC-129 facilitates long-range repulsive guidance of UNC-6 by enhancing UNC-5 + UNC-40 signaling at the expense of UNC-5 alone signaling through interaction with the UNC-5 receptor. This increases the set point sensitivity of growth cones to UNC-6/netrin as they simultaneously migrated up the UNC-129 gradient and down the UNC-6 gradient. Similar regulatory interactions between oppositely graded extracellular cues may be a common theme in guided cell and axon migrations.

SUBMITTER: MacNeil LT

PROVIDER: S-EPMC2745997 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways.

MacNeil Lesley T LT Hardy W Rod WR Pawson Tony T Wrana Jeffrey L JL Culotti Joseph G JG

Nature neuroscience 20090125 2

The UNC-5 receptor mediates axon repulsion from UNC-6/netrin through UNC-40 dependent (UNC-5 + UNC-40) and independent (UNC-5 alone) signaling pathways. It has been shown that UNC-40-dependent signaling is required for long-range repulsion of UNC-6/netrin; however, the mechanisms used to regulate distinct UNC-5 signaling pathways are poorly understood. We found that the C. elegans transforming growth factor beta (TGF-beta) family ligand UNC-129, graded opposite to UNC-6/netrin, functions indepen ...[more]

PMID: 19169249

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Dataset Information

UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways.

Publications

UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways.

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