UNC-6/Netrin induces neuronal asymmetry and defines the site of axon formation.
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.
Adler
Carolyn E
CE
Howard Hughes Medical Institute, Laboratory of Neural Circuits and Behavior, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Fetter
Richard D
RD
Bargmann
Cornelia I
CI
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity; D008055:Lipids; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000075385:Netrins; D009474:Neurons / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D008055:Lipids; C105812:Mig-10 protein, C elegans; D009419:Nerve Tissue Proteins; D000075385:Netrins; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans