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- Title
UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways.
- Authors
MacNeil, Lesley T.; Hardy, W. Rod; Pawson, Tony; Wrana, Jeffrey L.; Culotti, Joseph G.
- 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 β (TGF-β) family ligand UNC-129, graded opposite to UNC-6/netrin, functions independent of the canonical TGF-β 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.
- Subjects
AXONS; TRANSFORMING growth factors; GROWTH factors; CELL migration; IMMUNOMODULATORS; NEURONS; NERVOUS system
- Publication
Nature Neuroscience, 2009, Vol 12, Issue 2, p150
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn.2256