Nature Neuroscience 9, 511 - 518 (2006)
Published online: 5 March 2006; | doi:10.1038/nn1666
UNC-6/Netrin induces neuronal asymmetry and defines the site of axon formationCarolyn E Adler, Richard D Fetter
& Cornelia I Bargmann
Howard Hughes Medical Institute, Laboratory of Neural Circuits and Behavior, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Correspondence should be addressed to Cornelia I Bargmann cori@rockefeller.edu UNC-6/Netrin and its receptor UNC-40/DCC are conserved regulators of growth cone guidance. By directly observing developing neurons in vivo, we show that UNC-6 and UNC-40 also function during axon formation to initiate, maintain and orient asymmetric neuronal growth. The immature HSN neuron of Caenorhabditis elegans breaks spherical symmetry to extend a leading edge toward ventral UNC-6. In unc-6 and unc-40 mutants, leading edge formation fails, the cell remains symmetrical until late in development and the axon that eventually forms is misguided. Thus netrin has two activities: one that breaks neuronal symmetry and one that guides the future axon. As the axon forms, UNC-6, UNC-40 and the lipid modulators AGE-1/phosphoinositide 3-kinase (PI3K) and DAF-18/PTEN drive the actin-regulatory pleckstrin homology (PH) domain protein MIG-10/lamellipodin ventrally in HSN to promote asymmetric growth. The coupling of a directional netrin cue to sustained asymmetric growth via PI3K signaling is reminiscent of polarization in chemotaxing cells.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
