Gene Symbol: NetB
Description: Netrin-B
Alias: CG10521, CT29512, Dmel\CG10521, NETB, net, netB, netrin, netrin B, Netrin-B, CG10521-PA, CG10521-PB, CG10521-PC, CG10521-PD, CG10521-PE, CG10521-PF, CG10521-PG, D-netrin, D-netrin-B, NetB-PA, NetB-PB, NetB-PC, NetB-PD, NetB-PE, NetB-PF, NetB-PG, netrin, netrin B, netrin-B, netrinB
Species: fruit fly

Top Publications

  1. Chiba A. Early development of the Drosophila neuromuscular junction: a model for studying neuronal networks in development. Int Rev Neurobiol. 1999;43:1-24 pubmed
  2. Umemiya T, Takasu E, Takeichi M, Aigaki T, Nose A. Forked end: a novel transmembrane protein involved in neuromuscular specificity in drosophila identified by gain-of-function screening. J Neurobiol. 2002;51:205-14 pubmed
    ..During embryonic development, fend mRNA was detected in a subset of cells in the central nervous system and in the periphery. These results suggest that FEND is a novel axon guidance molecule involved in neuromuscular specificity. ..
  3. Liu Q, Hiramoto M, Ueda H, Gojobori T, Hiromi Y, Hirose S. Midline governs axon pathfinding by coordinating expression of two major guidance systems. Genes Dev. 2009;23:1165-70 pubmed publisher
    ..Midline is present on the promoter regions of these genes, indicating that Midline controls transcription directly. We propose that Midline controls axon pathfinding through coordinating the two guidance systems. ..
  4. Keleman K, Dickson B. Short- and long-range repulsion by the Drosophila Unc5 netrin receptor. Neuron. 2001;32:605-17 pubmed
    ..Here we report the identification of the Drosophila Unc5 receptor, and show that it is a repulsive Netrin receptor likely to contribute to motor axon guidance...
  5. Harris R, Sabatelli L, Seeger M. Guidance cues at the Drosophila CNS midline: identification and characterization of two Drosophila Netrin/UNC-6 homologs. Neuron. 1996;17:217-28 pubmed
    ..We have identified two Drosophila homologs of this protein family (Netrin-A and Netrin-B)...
  6. Furrer M, Kim S, Wolf B, Chiba A. Robo and Frazzled/DCC mediate dendritic guidance at the CNS midline. Nat Neurosci. 2003;6:223-30 pubmed
    ..single-cell labeling, we describe specific guidance defects in dendrites of identified neurons in frazzled, robo, netrin and commissureless mutant embryos of Drosophila melanogaster...
  7. Al Anzi B, Wyman R. The Drosophila immunoglobulin gene turtle encodes guidance molecules involved in axon pathfinding. Neural Dev. 2009;4:31 pubmed publisher
    ..Some of these molecules, such as the evolutionarily conserved netrin and slit proteins, are expressed in the embryonic midline, an area of extreme importance for early axon ..
  8. Newquist G, Drennan J, Lamanuzzi M, Walker K, Clemens J, Kidd T. Blocking apoptotic signaling rescues axon guidance in Netrin mutants. Cell Rep. 2013;3:595-606 pubmed publisher
    ..We uncover a mechanism for axon guidance by demonstrating that axons can accurately navigate in the absence of a Netrin gradient if apoptotic signaling is blocked...
  9. Labrador J, O keefe D, Yoshikawa S, McKinnon R, Thomas J, Bashaw G. The homeobox transcription factor even-skipped regulates netrin-receptor expression to control dorsal motor-axon projections in Drosophila. Curr Biol. 2005;15:1413-9 pubmed
    ..using genetics and single-cell mRNA-expression analysis, we show that expression and requirement of different Netrin receptor combinations correlate with distinct dorsal and ventral motor-axon projections in Drosophila...

More Information


  1. Yang L, Garbe D, Bashaw G. A frazzled/DCC-dependent transcriptional switch regulates midline axon guidance. Science. 2009;324:944-7 pubmed publisher
    ..Slit-roundabout repulsion and netrin-deleted in colorectal cancer (DCC) (frazzled) attraction must be tightly regulated to control midline axon ..
  2. Albrecht S, Altenhein B, Paululat A. The transmembrane receptor Uncoordinated5 (Unc5) is essential for heart lumen formation in Drosophila melanogaster. Dev Biol. 2011;350:89-100 pubmed publisher
    ..Our findings support the idea that Unc5 is crucial for lumen formation and thereby represents a repulsive cue acting during Drosophila heart tube formation. ..
  3. Hiramoto M, Hiromi Y. ROBO directs axon crossing of segmental boundaries by suppressing responsiveness to relocalized Netrin. Nat Neurosci. 2006;9:58-66 pubmed
    ..The initial trajectory of the longitudinal axons is guided by Netrin, which is localized on commissural axons by its receptor, Frazzled...
  4. Kuzina I, Song J, Giniger E. How Notch establishes longitudinal axon connections between successive segments of the Drosophila CNS. Development. 2011;138:1839-49 pubmed publisher
    ..This propels the axons as they establish the connection between successive segments. ..
  5. Spitzweck B, Brankatschk M, Dickson B. Distinct protein domains and expression patterns confer divergent axon guidance functions for Drosophila Robo receptors. Cell. 2010;140:409-20 pubmed publisher
    ..These data demonstrate how diversification of expression and structure within a single family of guidance receptors can shape complex patterns of neuronal wiring. ..
  6. Kolodziej P, Timpe L, Mitchell K, Fried S, Goodman C, Jan L, et al. frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance. Cell. 1996;87:197-204 pubmed
    ..The phenotypes strongly resemble those of a deletion of the two Drosophila Netrin genes...
  7. Garbe D, O Donnell M, Bashaw G. Cytoplasmic domain requirements for Frazzled-mediated attractive axon turning at the Drosophila midline. Development. 2007;134:4325-34 pubmed
    The conserved DCC ligand-receptor pair Netrin and Frazzled (Fra) has a well-established role in axon guidance. However, the specific sequence motifs required for orchestrating downstream signaling events are not well understood...
  8. Gong Q, Rangarajan R, Seeger M, Gaul U. The netrin receptor frazzled is required in the target for establishment of retinal projections in the Drosophila visual system. Development. 1999;126:1451-6 pubmed
    ..Our data suggest that Frazzled does not function as a Netrin receptor in attracting retinal fibers to the target; nor does it seem to act as a homotypic cell adhesion molecule...
  9. Manhire Heath R, Golenkina S, Saint R, Murray M. Netrin-dependent downregulation of Frazzled/DCC is required for the dissociation of the peripodial epithelium in Drosophila. Nat Commun. 2013;4:2790 pubmed publisher
    Netrins are secreted chemoattractants with roles in axon guidance, cell migration and epithelial plasticity. Netrin-1 also promotes the survival of metastasized cells by inhibiting the pro-apoptotic effects of its receptor Deleted in ..
  10. von Hilchen C, Hein I, Technau G, Altenhein B. Netrins guide migration of distinct glial cells in the Drosophila embryo. Development. 2010;137:1251-62 pubmed publisher
    ..We show that in Netrin mutants, two distinct populations of glial cells are affected: longitudinal glia (LG) fail to migrate medially in ..
  11. Brankatschk M, Dickson B. Netrins guide Drosophila commissural axons at short range. Nat Neurosci. 2006;9:188-94 pubmed
    ..Tethering endogenous netrin to the membrane selectively disrupts its long-range but not short-range activity, yet still allows normal ..
  12. Mitchell K, Doyle J, Serafini T, Kennedy T, Tessier Lavigne M, Goodman C, et al. Genetic analysis of Netrin genes in Drosophila: Netrins guide CNS commissural axons and peripheral motor axons. Neuron. 1996;17:203-15 pubmed
    Two tandem Netrin genes in Drosophila are expressed at the midline of the developing CNS and in different subsets of neurons, muscles, and epidermal patches...
  13. Hiramoto M, Hiromi Y, Giniger E, Hotta Y. The Drosophila Netrin receptor Frazzled guides axons by controlling Netrin distribution. Nature. 2000;406:886-9 pubmed
    b>Netrin is a secreted protein that can act as a chemotropic axon guidance cue...
  14. Winberg M, Mitchell K, Goodman C. Genetic analysis of the mechanisms controlling target selection: complementary and combinatorial functions of netrins, semaphorins, and IgCAMs. Cell. 1998;93:581-91 pubmed
    ..recognize their appropriate muscle targets were dissected using Drosophila genetics to add or subtract Netrin A, Netrin B, Semaphorin II, and Fasciclin II alone or in combination...
  15. Andrews G, Tanglao S, Farmer W, Morin S, Brotman S, Berberoglu M, et al. Dscam guides embryonic axons by Netrin-dependent and -independent functions. Development. 2008;135:3839-48 pubmed publisher
    Developing axons are attracted to the CNS midline by Netrin proteins and other as yet unidentified signals. Netrin signals are transduced in part by Frazzled (Fra)/DCC receptors...
  16. Brierley D, Blanc E, Reddy O, Vijayraghavan K, Williams D. Dendritic targeting in the leg neuropil of Drosophila: the role of midline signalling molecules in generating a myotopic map. PLoS Biol. 2009;7:e1000199 pubmed publisher
    ..of motoneuron dendrites in the leg neuropil is controlled by the midline signalling systems Slit-Robo and Netrin-Fra...
  17. Tear G. Axon guidance at the central nervous system midline. Cell Mol Life Sci. 1999;55:1365-76 pubmed
    ..In this way, axons extend toward or away from the midline and those that do cross change their behaviour to respond to longitudinal signals on the contralateral side. ..
  18. Morikawa R, Kanamori T, Yasunaga K, Emoto K. Different levels of the Tripartite motif protein, Anomalies in sensory axon patterning (Asap), regulate distinct axonal projections of Drosophila sensory neurons. Proc Natl Acad Sci U S A. 2011;108:19389-94 pubmed publisher
    ..We also show by biochemical and genetic analysis that Asap regulates Netrin signaling, at least in part by linking the Netrin receptor Frazzled to the downstream effector Pico...
  19. Halachmi N, Nachman A, Salzberg A. A newly identified type of attachment cell is critical for normal patterning of chordotonal neurons. Dev Biol. 2016;411:61-71 pubmed publisher
  20. Timofeev K, Joly W, Hadjieconomou D, Salecker I. Localized netrins act as positional cues to control layer-specific targeting of photoreceptor axons in Drosophila. Neuron. 2012;75:80-93 pubmed publisher
    ..b>Netrin-B is specifically localized in this layer owing to axonal release by lamina neurons L3 and capture by target ..
  21. Akin O, Zipursky S. Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system. elife. 2016;5: pubmed publisher
    ..The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical ..
  22. Onel S, Bolke L, Klämbt C. The Drosophila ARF6-GEF Schizo controls commissure formation by regulating Slit. Development. 2004;131:2587-94 pubmed
    ..Two evolutionarily conserved signaling molecules, Netrin and Slit, are expressed in the CNS midline cells...
  23. Chotard C, Salecker I. Neurons and glia: team players in axon guidance. Trends Neurosci. 2004;27:655-61 pubmed
    ..Equally, neurons provide crucial information to glia, supporting their migration and correct positioning. ..
  24. Cate M, Gajendra S, Alsbury S, Raabe T, Tear G, Mitchell K. Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila. Development. 2016;143:972-7 pubmed publisher
    ..Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline...
  25. Simanton W, Clark S, Clemons A, Jacowski C, Farrell VanZomeren A, Beach P, et al. Conservation of arthropod midline netrin accumulation revealed with a cross-reactive antibody provides evidence for midline cell homology. Evol Dev. 2009;11:260-8 pubmed publisher
    ..These comparative analyses were aided by a cross-reactive antibody generated against the Netrin (Net) protein, a midline cell marker and regulator of axonogenesis...
  26. Hughes S, Salinas P. Control of muscle fibre and motoneuron diversification. Curr Opin Neurobiol. 1999;9:54-64 pubmed
    ..We propose a model in which four classes of decision control the patterning of both motoneurons and muscles. ..
  27. Pecot M, Chen Y, Akin O, Chen Z, Tsui C, Zipursky S. Sequential axon-derived signals couple target survival and layer specificity in the Drosophila visual system. Neuron. 2014;82:320-33 pubmed publisher
    ..L3 axons then produce Netrin, which regulates the layer-specific targeting of another neuron within the same circuit...
  28. Orr B, Borgen M, Caruccio P, Murphey R. Netrin and Frazzled regulate presynaptic gap junctions at a Drosophila giant synapse. J Neurosci. 2014;34:5416-30 pubmed publisher
    b>Netrin and its receptor, Frazzled, dictate the strength of synaptic connections in the giant fiber system (GFS) of Drosophila melanogaster by regulating gap junction localization in the presynaptic terminal...
  29. O Donnell M, Bashaw G. Distinct functional domains of the Abelson tyrosine kinase control axon guidance responses to Netrin and Slit to regulate the assembly of neural circuits. Development. 2013;140:2724-33 pubmed publisher
    ..We identified Abl in a genetic screen for genes that contribute to Netrin-dependent axon guidance in midline-crossing (commissural) neurons...
  30. Hummel T, Schimmelpfeng K, Klämbt C. Commissure formation in the embryonic CNS of Drosophila. Development. 1999;126:771-9 pubmed
    ..Here we present evidence that beside the previously known NETRIN/FRAZZLED (DCC) signalling system an additional attractive system(s) is operating in the developing embryonic ..
  31. Tear G. Neuronal guidance. A genetic perspective. Trends Genet. 1999;15:113-8 pubmed
    ..Here I highlight the part genetic screens and analyses have played in revealing some of the key players in neuronal guidance. ..
  32. Dorsten J, Varughese B, Karmo S, Seeger M, VanBerkum M. In the absence of frazzled over-expression of Abelson tyrosine kinase disrupts commissure formation and causes axons to leave the embryonic CNS. PLoS ONE. 2010;5:e9822 pubmed publisher
    In the Drosophila embryonic nerve cord, the formation of commissures require both the chemoattractive Netrin receptor Frazzled (Fra) and the Abelson (Abl) cytoplasmic tyrosine kinase...
  33. Bhat K. Slit-roundabout signaling neutralizes netrin-Frazzled-mediated attractant cue to specify the lateral positioning of longitudinal axon pathways. Genetics. 2005;170:149-59 pubmed
    ..that in the Drosophila nerve cord the growth cones of longitudinal tracts are subjected to attraction by the Netrin-Frazzled pathway...
  34. Guthrie S. Axon guidance: netrin receptors are revealed. Curr Biol. 1997;7:R6-9 pubmed
    ..Now, members of a family of netrin receptors have been identified in all three animal groups and shown to have crucial, conserved roles in axon ..
  35. Terman J, Kolodkin A. Attracted or repelled? Look within. Neuron. 1999;23:193-5 pubmed
  36. Organisti C, Hein I, Grunwald Kadow I, Suzuki T. Flamingo, a seven-pass transmembrane cadherin, cooperates with Netrin/Frazzled in Drosophila midline guidance. Genes Cells. 2015;20:50-67 pubmed publisher
    ..In Drosophila, commissural axons sense the midline attractants Netrin A and B (Net) through Frazzled (Fra) receptors...
  37. Bhat K, Gaziova I, Krishnan S. Regulation of axon guidance by slit and netrin signaling in the Drosophila ventral nerve cord. Genetics. 2007;176:2235-46 pubmed
    b>Netrin and Slit signaling systems play opposing roles during the positioning of longitudinal tracts along the midline in the ventral nerve cord of Drosophila embryo...
  38. O Donnell M, Bashaw G. Src inhibits midline axon crossing independent of Frazzled/Deleted in Colorectal Carcinoma (DCC) receptor tyrosine phosphorylation. J Neurosci. 2013;33:305-14 pubmed publisher
    The phylogenetically conserved Netrin family of chemoattractants signal outgrowth and attractive turning of commissural axons through the Deleted in Colorectal Carcinoma (DCC) family of receptors...
  39. Eisen J. Genetic and molecular analyses of motoneuron development. Curr Opin Neurobiol. 1998;8:697-704 pubmed
    ..Many of the same molecules participate in the guidance of both vertebrate and fly motor axons. It is less clear, however, whether the same molecular mechanisms establish vertebrate and fly motoneuron identities. ..
  40. Drescher U. Netrins find their receptor. Nature. 1996;384:416-7 pubmed
  41. Kolesnikov T, Beckendorf S. NETRIN and SLIT guide salivary gland migration. Dev Biol. 2005;284:102-11 pubmed
    ..Here, we show that at least two of these axon guidance molecules, NETRIN and SLIT, act through their canonical receptors, to guide Drosophila embryonic salivary glands...
  42. Gupta T, Giangrande A. Collective cell migration: "all for one and one for all". J Neurogenet. 2014;28:190-8 pubmed publisher
    ..This review impinges upon the cellular and molecular interactions underlying collective cell migration in animal models, and highlights the recent advances made through in vivo analyses of the Drosophila wing glia. ..
  43. Enright A, John B, Gaul U, Tuschl T, Sander C, Marks D. MicroRNA targets in Drosophila. Genome Biol. 2003;5:R1 pubmed
    ..The target prediction algorithm is freely available and can be applied to whole genome sequences using identified miRNA sequences. ..
  44. Newquist G, Hogan J, Walker K, Lamanuzzi M, Bowser M, Kidd T. Control of male and female fertility by the netrin axon guidance genes. PLoS ONE. 2013;8:e72524 pubmed publisher
    The netrin axon guidance genes have previously been implicated in fertility in C. elegans and in vertebrates...
  45. Matthews B, Grueber W. Dscam1-mediated self-avoidance counters netrin-dependent targeting of dendrites in Drosophila. Curr Biol. 2011;21:1480-7 pubmed publisher that Dscam1 functions to counter Drosophila sensory neuron dendritic targeting signals provided by secreted Netrin-B and Frazzled, a netrin receptor...
  46. Brose K, Tessier Lavigne M. Slit proteins: key regulators of axon guidance, axonal branching, and cell migration. Curr Opin Neurobiol. 2000;10:95-102 pubmed
  47. Sano H, Renault A, Lehmann R. Control of lateral migration and germ cell elimination by the Drosophila melanogaster lipid phosphate phosphatases Wunen and Wunen 2. J Cell Biol. 2005;171:675-83 pubmed
    ..Our results suggest that expression of wun/wun-2 repellents along the migratory paths provides faithful control over the sorting of PGCs into two gonads and eliminates PGCs left in the middle of the embryo. ..
  48. Pert M, Gan M, Saint R, Murray M. Netrins and Frazzled/DCC promote the migration and mesenchymal to epithelial transition of Drosophila midgut cells. Biol Open. 2015;4:233-43 pubmed publisher
    ..Both netrinA and netrinB are expressed in the visceral mesoderm, the substrate upon which midgut cells migrate, while their receptor ..
  49. Alavi M, Song M, King G, Gillis T, Propst R, Lamanuzzi M, et al. Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons. PLoS Biol. 2016;14:e1002560 pubmed publisher
    ..The ability of Dscam1 to modify the output of other receptors in a ligand-dependent fashion may be a general principle for Dscam proteins. ..
  50. Giger R, Kolodkin A. Frazzled precision guides axons. Nature. 2000;406:841, 843 pubmed
  51. Noordermeer J, Kopczynski C, Fetter R, Bland K, Chen W, Goodman C. Wrapper, a novel member of the Ig superfamily, is expressed by midline glia and is required for them to ensheath commissural axons in Drosophila. Neuron. 1998;21:991-1001 pubmed
    ..However, they do not ensheath the commissural axons, and as a result, the glia die. In the absence of Wrapper, the two axon commissures are not properly separated. ..
  52. Jan Y, Jan L. The control of dendrite development. Neuron. 2003;40:229-42 pubmed
    ..In contrast, the control of dendrite development is still much less well understood. However, recent progress has begun to shed light on the molecular mechanisms that orchestrate dendrite growth, arborization, and guidance. ..
  53. Mrkusich E, Osman Z, Bates K, Marchingo J, Duman Scheel M, Whitington P. Netrin-guided accessory cell morphogenesis dictates the dendrite orientation and migration of a Drosophila sensory neuron. Development. 2010;137:2227-35 pubmed publisher
    ..Cap cell morphogenesis is regulated by Netrin-A, which is produced by epidermal cells at the destination of the cap cell process...
  54. Hakeda Suzuki S, Suzuki T. Cell surface control of the layer specific targeting in the Drosophila visual system. Genes Genet Syst. 2014;89:9-15 pubmed
    ..Fundamental and comprehensive understanding of the crosstalk of growing axons and target regions in the Drosophila optic lobe will elucidate the general principles applicable to more complex nervous systems. ..
  55. Long S, Fulkerson E, Breese R, Hernández G, Davis C, Melton M, et al. A comparison of midline and tracheal gene regulation during Drosophila development. PLoS ONE. 2014;9:e85518 pubmed publisher
    ..Taken together, these experiments identify elements overrepresented within midline and tracheal enhancers and suggest that sequences immediately surrounding a CME help dictate whether a gene is expressed in the midline or trachea. ..
  56. Seeger M, Beattie C. Attraction versus repulsion: modular receptors make the difference in axon guidance. Cell. 1999;97:821-4 pubmed
  57. Blader -. Oh, for some simple guidance. Trends Genet. 2000;16:486 pubmed
  58. Macabenta F, Jensen A, Cheng Y, Kramer J, Kramer S. Frazzled/DCC facilitates cardiac cell outgrowth and attachment during Drosophila dorsal vessel formation. Dev Biol. 2013;380:233-42 pubmed publisher
    ..Previous studies have shown that the Slit/Roundabout and Netrin/Unc5 repulsive signaling pathways facilitate site-specific loss of adhesion between contralateral CBs in order to ..
  59. Sun Q, Bahri S, Schmid A, Chia W, Zinn K. Receptor tyrosine phosphatases regulate axon guidance across the midline of the Drosophila embryo. Development. 2000;127:801-12 pubmed