Gene Symbol: unc-6
Description: Netrin unc-6
Alias: Netrin unc-6
Species: Caenorhabditis elegans

Top Publications

  1. Ziel J, Hagedorn E, Audhya A, Sherwood D. UNC-6 (netrin) orients the invasive membrane of the anchor cell in C. elegans. Nat Cell Biol. 2009;11:183-9 pubmed publisher
    ..Together, these results characterize an invasive membrane domain in vivo, and reveal a role for UNC-6 (netrin) in polarizing this domain towards its basement membrane target. ..
  2. Chan S, Zheng H, Su M, Wilk R, Killeen M, Hedgecock E, et al. UNC-40, a C. elegans homolog of DCC (Deleted in Colorectal Cancer), is required in motile cells responding to UNC-6 netrin cues. Cell. 1996;87:187-95 pubmed
    ..Together with the recent report that DCC is a netrin receptor in vertebrates, our results suggest that UNC-40 is a component of UNC-6 receptors on motile cells. ..
  3. Asakura T, Ogura K, Goshima Y. UNC-6 expression by the vulval precursor cells of Caenorhabditis elegans is required for the complex axon guidance of the HSN neurons. Dev Biol. 2007;304:800-10 pubmed
    ..These results suggest that UNC-6 expressed by the VPC and the VNC cooperatively regulates the complex HSN axon guidance. ..
  4. Quinn C, Pfeil D, Chen E, Stovall E, Harden M, Gavin M, et al. UNC-6/netrin and SLT-1/slit guidance cues orient axon outgrowth mediated by MIG-10/RIAM/lamellipodin. Curr Biol. 2006;16:845-53 pubmed
    ..The attractive and repulsive guidance cues orient MIG-10-dependant axon outgrowth to cause a directional response. ..
  5. Adler C, Fetter R, Bargmann C. UNC-6/Netrin induces neuronal asymmetry and defines the site of axon formation. Nat Neurosci. 2006;9:511-8 pubmed
    ..The coupling of a directional netrin cue to sustained asymmetric growth via PI3K signaling is reminiscent of polarization in chemotaxing cells. ..
  6. Xu Z, Li H, Wadsworth W. The roles of multiple UNC-40 (DCC) receptor-mediated signals in determining neuronal asymmetry induced by the UNC-6 (netrin) ligand. Genetics. 2009;183:941-9 pubmed publisher
    ..The UNC-40 ectodomain mutation activates the polarization signal, whereas different forms of the UNC-6 ligand produce UNC-40 conformational changes that allow or prohibit the orientation signal. ..
  7. Norris A, Lundquist E. UNC-6/netrin and its receptors UNC-5 and UNC-40/DCC modulate growth cone protrusion in vivo in C. elegans. Development. 2011;138:4433-42 pubmed publisher
    ..g. filopodial) protrusion...
  8. Wadsworth W, Bhatt H, Hedgecock E. Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin cues for guiding migrations in C. elegans. Neuron. 1996;16:35-46 pubmed
    ..EGF-like module V-2 is essential for dorsal guidance activity; we infer this module is important for interactions between UNC-6 and the dorsal guidance receptor UNC-5. ..
  9. COLON RAMOS D, Margeta M, Shen K. Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans. Science. 2007;318:103-6 pubmed
    ..These results indicate that netrin can be used both for guidance and local synaptogenesis and suggest that glial cells can function as guideposts during the assembly of neural circuits in vivo. ..

More Information


  1. Hao J, Adler C, Mebane L, Gertler F, Bargmann C, Tessier Lavigne M. The tripartite motif protein MADD-2 functions with the receptor UNC-40 (DCC) in Netrin-mediated axon attraction and branching. Dev Cell. 2010;18:950-60 pubmed publisher
  2. Quinn C, Pfeil D, Wadsworth W. CED-10/Rac1 mediates axon guidance by regulating the asymmetric distribution of MIG-10/lamellipodin. Curr Biol. 2008;18:808-13 pubmed publisher
    ..We propose that the interaction between activated CED-10/Rac1 and MIG-10/lamellipodin triggers local cytoskeletal assembly and polarizes outgrowth activity in response to UNC-6/netrin. ..
  3. Poon V, Klassen M, Shen K. UNC-6/netrin and its receptor UNC-5 locally exclude presynaptic components from dendrites. Nature. 2008;455:669-73 pubmed publisher
  4. Hedgecock E, Culotti J, Hall D. The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron. 1990;4:61-85 pubmed
    ..These genes probably identify molecular cues on the basal lamina that guide mesodermal migrations. The same basal lamina cues, or perhaps related molecules on the epidermal cell surfaces, guide pioneer neurons. ..
  5. Song S, Ge Q, Wang J, Chen H, Tang S, Bi J, et al. TRIM-9 functions in the UNC-6/UNC-40 pathway to regulate ventral guidance. J Genet Genomics. 2011;38:1-11 pubmed publisher
    ..Over-expression of the Netrin/UNC-6 receptor Frazzled suppresses the guidance defects in trim-9 mutants. Our study reveals an evolutionarily conserved function of TRIM-9 in the UNC-40/Frazzled-mediated UNC-6/Netrin attraction pathway. ..
  6. Asakura T, Ogura K, Goshima Y. IRE-1/XBP-1 pathway of the unfolded protein response is required for properly localizing neuronal UNC-6/Netrin for axon guidance in C. elegans. Genes Cells. 2015;20:153-9 pubmed publisher
    ..We propose that the proper secretion of UNC-6/Netrin from the ventral neurons requires the activity of IRE-1. ..
  7. Blanchette C, Perrat P, Thackeray A, Bénard C. Glypican Is a Modulator of Netrin-Mediated Axon Guidance. PLoS Biol. 2015;13:e1002183 pubmed publisher
    ..We propose that LON-2/glypican acts as a modulator of UNC-40/DCC-mediated guidance to fine-tune axonal responses to UNC-6/netrin signals during migration. ..
  8. Florica R, Hipolito V, Bautista S, Anvari H, Rapp C, El Rass S, et al. The ENU-3 protein family members function in the Wnt pathway parallel to UNC-6/Netrin to promote motor neuron axon outgrowth in C. elegans. Dev Biol. 2017;430:249-261 pubmed publisher
    ..We conclude that the ENU-3 family proteins function in a pathway parallel to the UNC-6/Netrin pathway for motor neuron axon outgrowth, most likely in the Wnt pathway. ..
  9. Barsi Rhyne B, Miller K, Vargas C, Thomas A, Park J, Bremer M, et al. Kinesin-1 acts with netrin and DCC to maintain sensory neuron position in Caenorhabditis elegans. Genetics. 2013;194:175-87 pubmed publisher
    ..Our findings suggest an active posterior cell migration mediated by UNC-116/KHC occurs throughout development to maintain proper PHB cell body position and define a new pathway that mediates maintenance of neuronal cell body position. ..
  10. Unsoeld T, Park J, Hutter H. Discoidin domain receptors guide axons along longitudinal tracts in C. elegans. Dev Biol. 2013;374:142-52 pubmed publisher
    ..Our results provide the first insight on discoidin domain receptor function in invertebrates and establish a novel role for discoidin domain receptors in axon navigation and axon tract formation. ..
  11. Gujar M, Stricker A, Lundquist E. Flavin monooxygenases regulate Caenorhabditis elegans axon guidance and growth cone protrusion with UNC-6/Netrin signaling and Rac GTPases. PLoS Genet. 2017;13:e1006998 pubmed publisher
    ..From these studies we conclude that FMO-1, FMO-4, FMO-5, and EHBP-1 represent new players downstream of UNC-6/Netrin receptors and Rac GTPases that inhibit growth cone filopodial protrusion in repulsive axon guidance. ..
  12. Jia L, Emmons S. Genes that control ray sensory neuron axon development in the Caenorhabditis elegans male. Genetics. 2006;173:1241-58 pubmed
    ..This system is applicable to the study of mechanisms underlying topographic mapping of sensory neurons into target circuitry where the next stage of information processing is carried out. ..
  13. Dixon S, Alexander M, Fernandes R, Ricker N, Roy P. FGF negatively regulates muscle membrane extension in Caenorhabditis elegans. Development. 2006;133:1263-75 pubmed
    ..Our data are consistent with a model in which integrins and laminins are needed for directed muscle arm extension to the nerve cords, while FGF signaling provides a general mechanism to regulate muscle membrane extension. ..
  14. Mörck C, Axäng C, Pilon M. A genetic analysis of axon guidance in the C elegans pharynx. Dev Biol. 2003;260:158-75 pubmed
    ..We isolated five novel mutants in a screen for worms exhibiting abnormal morphology of the M2 neurons. These mutants define a new gene class designated mnm (M neuron morphology abnormal). ..
  15. Yee C, Sybingco S, Serdetchania V, Kholkina G, Bueno de Mesquita M, Naqvi Z, et al. ENU-3 is a novel motor axon outgrowth and guidance protein in C. elegans. Dev Biol. 2011;352:243-53 pubmed publisher
    ..We conclude that ENU-3 is a novel C. elegans protein that affects both motor axon outgrowth and guidance. ..
  16. Dalpé G, Zheng H, Brown L, Culotti J. Semaphorin-1 and netrin signal in parallel and permissively to position the male ray 1 sensillum in Caenorhabditis elegans. Genetics. 2012;192:959-71 pubmed publisher
    ..Several lines of evidence indicate that SMP-1 and UNC-6 function permissively in the context of ray 1 positioning. ..
  17. Xu Y, Quinn C. MIG-10 functions with ABI-1 to mediate the UNC-6 and SLT-1 axon guidance signaling pathways. PLoS Genet. 2012;8:e1003054 pubmed publisher
    ..Together, these observations suggest that MIG-10 interacts with ABI-1 and WVE-1 to mediate the UNC-6 and SLT-1 guidance pathways...
  18. Chen C, He C, Liao C, Pan C. A Wnt-planar polarity pathway instructs neurite branching by restricting F-actin assembly through endosomal signaling. PLoS Genet. 2017;13:e1006720 pubmed publisher
    ..Our study provides insights for how attractive and repulsive signals coordinate to sculpt neurite branching patterns, which are critical for circuit connectivity. ..
  19. Wang Z, Linden L, Naegeli K, Ziel J, Chi Q, Hagedorn E, et al. UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity. J Cell Biol. 2014;206:619-33 pubmed publisher
    ..Together, our data suggest that UNC-6 (netrin) directs polarized responses by stabilizing UNC-40 clustering. We propose that ligand-independent UNC-40 clustering provides a robust and adaptable mechanism to polarize toward netrin. ..
  20. Desai C, Garriga G, McIntire S, Horvitz H. A genetic pathway for the development of the Caenorhabditis elegans HSN motor neurons. Nature. 1988;336:638-46 pubmed
    ..Nearly all are pleiotropic, revealing that the genes specifying HSN development also function in the development of other cell types. ..
  21. Dalpé G, Tarsitano M, Persico M, Zheng H, Culotti J. C. elegans PVF-1 inhibits permissive UNC-40 signalling through CED-10 GTPase to position the male ray 1 sensillum. Development. 2013;140:4020-30 pubmed publisher
    ..These data report the first case of VEGF-induced inhibition of the netrin signalling and a molecular conservation of VEGF function from worms to humans. ..
  22. Lee J, Li W, Guan K. SRC-1 mediates UNC-5 signaling in Caenorhabditis elegans. Mol Cell Biol. 2005;25:6485-95 pubmed
  23. Teichmann H, Shen K. UNC-6 and UNC-40 promote dendritic growth through PAR-4 in Caenorhabditis elegans neurons. Nat Neurosci. 2011;14:165-72 pubmed publisher
    ..These data suggest that axon and dendrite of one neuron interpret common environmental cues with different receptors and downstream signaling pathways. ..
  24. Colavita A, Culotti J. Suppressors of ectopic UNC-5 growth cone steering identify eight genes involved in axon guidance in Caenorhabditis elegans. Dev Biol. 1998;194:72-85 pubmed
    ..Several of these mutations cause axon guidance defects similar to those found in unc-5 mutants. We propose that some or all of these genes may function in a developmentally important unc-5 signaling pathway. ..
  25. Nishiwaki K, Hisamoto N, Matsumoto K. A metalloprotease disintegrin that controls cell migration in Caenorhabditis elegans. Science. 2000;288:2205-8 pubmed
    ..This localization is dependent on the disintegrin-like domain of MIG-17 and its catalytic activity. These results suggest that the MIG-17 metalloprotease directs migration of DTCs by remodeling the basement membrane. ..
  26. Smith C, WATSON J, VanHoven M, COLON RAMOS D, Miller D. Netrin (UNC-6) mediates dendritic self-avoidance. Nat Neurosci. 2012;15:731-7 pubmed publisher
    ..Our findings offer a new model for how an evolutionarily conserved morphogenic cue and its cognate receptors can pattern a fundamental feature of dendritic architecture. ..
  27. Kulkarni G, Li H, Wadsworth W. CLEC-38, a transmembrane protein with C-type lectin-like domains, negatively regulates UNC-40-mediated axon outgrowth and promotes presynaptic development in Caenorhabditis elegans. J Neurosci. 2008;28:4541-50 pubmed publisher
    ..We suggest CLEC-38 plays a role in promoting synapse assembly and refining axon outgrowth activity. ..
  28. Yang Y, Lee W, Tang X, Wadsworth W. Extracellular matrix regulates UNC-6 (netrin) axon guidance by controlling the direction of intracellular UNC-40 (DCC) outgrowth activity. PLoS ONE. 2014;9:e97258 pubmed publisher
    ..Together, these results suggest that an extracellular matrix can regulate the direction of UNC-6 guidance by increasing the probability that UNC-40-mediated axon outgrowth activity will be oriented in a specific direction. ..
  29. Yee C, Florica R, Fillingham J, Killeen M. ENU-3 functions in an UNC-6/netrin dependent pathway parallel to UNC-40/DCC/frazzled for outgrowth and guidance of the touch receptor neurons in C. elegans. Dev Dyn. 2014;243:459-67 pubmed publisher
    ..Motor neuron axon outgrowth defects are caused by the presence of UNC-40 and the absence of functional UNC-5 or UNC-6 and defects are enhanced by the absence of functional ENU-3. ..
  30. Chang C, Yu T, Bargmann C, Tessier Lavigne M. Inhibition of netrin-mediated axon attraction by a receptor protein tyrosine phosphatase. Science. 2004;305:103-6 pubmed
    ..The known effects of other RPTPs in axon guidance could result from modulation of guidance receptors like UNC-40/DCC. ..