Gene Symbol: unc-40
Description: hypothetical protein
Species: Caenorhabditis elegans

Top Publications

  1. 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. ..
  2. 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
  3. 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...
  4. Zallen J, Kirch S, Bargmann C. Genes required for axon pathfinding and extension in the C. elegans nerve ring. Development. 1999;126:3679-92 pubmed
    ..Together, these genes define pathways required for axon growth, guidance and maintenance during nervous system development. ..
  5. Yu T, Hao J, Lim W, Tessier Lavigne M, Bargmann C. Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function. Nat Neurosci. 2002;5:1147-54 pubmed
    ..A combinatorial logic dictates alternative functions for UNC-40/DCC, which can act in attraction to UNC-6/Netrin, repulsion from Netrin (with UNC-5), or repulsion from Slit (with SAX-3). ..
  6. Sundararajan L, Lundquist E. Transmembrane proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 control anterior-posterior neuroblast migration with left-right functional asymmetry in Caenorhabditis elegans. Genetics. 2012;192:1373-88 pubmed publisher
    ..These studies indicate an inherent left-right asymmetry in the Q neuroblasts with regard to UNC-40, PTP-3, and MIG-21 function that results in posterior vs. anterior migration. ..
  7. 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. ..
  8. Alexander M, Chan K, Byrne A, Selman G, Lee T, Ono J, et al. An UNC-40 pathway directs postsynaptic membrane extension in Caenorhabditis elegans. Development. 2009;136:911-22 pubmed publisher
    ..Our work is the first to define a pathway for directed muscle membrane extension and illustrates that axon guidance components can play key roles in postsynaptic membrane expansion. ..
  9. Alexander M, Selman G, Seetharaman A, Chan K, D Souza S, Byrne A, et al. MADD-2, a homolog of the Opitz syndrome protein MID1, regulates guidance to the midline through UNC-40 in Caenorhabditis elegans. Dev Cell. 2010;18:961-72 pubmed publisher
    ..The analogous phenotypes that result from MADD-2 and MID1 mutations suggest that C1-TRIM proteins may have a conserved biological role in midline-oriented developmental events. ..

More Information


  1. Hagedorn E, Ziel J, Morrissey M, Linden L, Wang Z, Chi Q, et al. The netrin receptor DCC focuses invadopodia-driven basement membrane transmigration in vivo. J Cell Biol. 2013;201:903-13 pubmed publisher
    ..These studies reveal an UNC-40-mediated morphogenetic transition at the cell-basement membrane interface that directs invading cells across basement membrane barriers...
  2. 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. ..
  3. Demarco R, Struckhoff E, Lundquist E. The Rac GTP exchange factor TIAM-1 acts with CDC-42 and the guidance receptor UNC-40/DCC in neuronal protrusion and axon guidance. PLoS Genet. 2012;8:e1002665 pubmed publisher
    ..Our results also suggest that Rac GTPase activity is controlled by different GEFs in distinct axon guidance contexts, explaining how Rac GTPases can specifically control multiple cellular functions. ..
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. 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. ..
  8. 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. ..
  9. MacNeil L, Hardy W, Pawson T, Wrana J, Culotti J. UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways. Nat Neurosci. 2009;12:150-5 pubmed publisher
    ..Similar regulatory interactions between oppositely graded extracellular cues may be a common theme in guided cell and axon migrations. ..
  10. Tang X, Wadsworth W. SAX-3 (Robo) and UNC-40 (DCC) regulate a directional bias for axon guidance in response to multiple extracellular cues. PLoS ONE. 2014;9:e110031 pubmed publisher
    ..The probability distribution for each neuron is determined by the collective effect of all the cues. Since the sum of the probabilities must equal one, each cue affects the probability of outgrowth in multiple directions. ..
  11. Axäng C, Rauthan M, Hall D, Pilon M. Developmental genetics of the C. elegans pharyngeal neurons NSML and NSMR. BMC Dev Biol. 2008;8:38 pubmed publisher
    ..Together with the guidance of the M2 neuron, this is the second case of a pharyngeal neuron establishing one of its processes using an unexpected mechanism. ..
  12. Lee J, Li W, Guan K. SRC-1 mediates UNC-5 signaling in Caenorhabditis elegans. Mol Cell Biol. 2005;25:6485-95 pubmed
  13. Wang L, Liu Z, Shi H, Liu J. Two Paralogous Tetraspanins TSP-12 and TSP-14 Function with the ADAM10 Metalloprotease SUP-17 to Promote BMP Signaling in Caenorhabditis elegans. PLoS Genet. 2017;13:e1006568 pubmed publisher
    ..We also provide genetic evidence showing that a known BMP signaling modulator, UNC-40/neogenin/DCC, is one of the substrates of SUP-17/ADAM10 in the BMP signaling pathway. ..
  14. Norris A, Sundararajan L, Morgan D, Roberts Z, Lundquist E. The UNC-6/Netrin receptors UNC-40/DCC and UNC-5 inhibit growth cone filopodial protrusion via UNC-73/Trio, Rac-like GTPases and UNC-33/CRMP. Development. 2014;141:4395-405 pubmed publisher
  15. 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. ..
  16. 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. ..
  17. 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. ..
  18. Li P, Collins K, Koelle M, Shen K. LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans. elife. 2013;2:e00378 pubmed publisher
    ..Therefore, the LIN-12/Notch signaling specifies target selection by selectively up-regulating guidance molecules and forming muscle arms in target cells. DOI:http://dx.doi.org/10.7554/eLife.00378.001. ..
  19. Middelkoop T, Williams L, Yang P, Luchtenberg J, Betist M, Ji N, et al. The thrombospondin repeat containing protein MIG-21 controls a left-right asymmetric Wnt signaling response in migrating C. elegans neuroblasts. Dev Biol. 2012;361:338-48 pubmed publisher
    ..We conclude that MIG-21 and UNC-40 control the asymmetry in Wnt signaling response by restricting posterior polarization to one of the two Q neuroblasts. ..
  20. Xu Y, Taru H, Jin Y, Quinn C. SYD-1C, UNC-40 (DCC) and SAX-3 (Robo) function interdependently to promote axon guidance by regulating the MIG-2 GTPase. PLoS Genet. 2015;11:e1005185 pubmed publisher
    ..Our observations reveal a molecular mechanism that can allow two guidance receptors to function interdependently to regulate a common downstream effector, providing a potential means for the integration of guidance signals. ..
  21. Tian C, Shi H, Xiong S, Hu F, Xiong W, Liu J. The neogenin/DCC homolog UNC-40 promotes BMP signaling via the RGM protein DRAG-1 in C. elegans. Development. 2013;140:4070-80 pubmed publisher
    ..Mouse neogenin lacking the intracellular domain is also capable of mediating BMP signaling. These findings reveal an unexpected mode of action for neogenin regulation of BMP signaling. ..
  22. 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. ..
  23. Liu Z, Shi H, Szymczak L, Aydin T, Yun S, Constas K, et al. Promotion of bone morphogenetic protein signaling by tetraspanins and glycosphingolipids. PLoS Genet. 2015;11:e1005221 pubmed publisher
  24. Olsson Carter K, Slack F. A developmental timing switch promotes axon outgrowth independent of known guidance receptors. PLoS Genet. 2010;6: pubmed publisher
    ..This developmental switch depends neither on the UNC-40/DCC and SAX-3/Robo receptors nor on the direction of axon growth, demonstrating that it acts independently of ventral guidance signals to control the timing of HSN axon elongation. ..
  25. 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. ..
  26. Chan K, Seetharaman A, Bagg R, Selman G, Zhang Y, Kim J, et al. EVA-1 functions as an UNC-40 Co-receptor to enhance attraction to the MADD-4 guidance cue in Caenorhabditis elegans. PLoS Genet. 2014;10:e1004521 pubmed publisher
    ..By enabling UNC-40 to respond to MADD-4 in the presence of UNC-6, EVA-1 may increase the precision by which UNC-40-directed processes can reach their MADD-4-expressing targets within a field of the UNC-6 guidance cue. ..