Gene Symbol: NetA
Description: Netrin-A
Alias: CG18657, CT27014, Dmel\CG18657, NetrinA, net, netA, netrin, netrin A, Netrin-A, CG18657-PA, CG18657-PB, CG18657-PC, D-netrin, D-netrin-A, NetA-PA, NetA-PB, NetA-PC, NetrinA, netrin, netrin A
Species: fruit fly

Top Publications

  1. VanZomeren Dohm A, Flannery E, Duman Scheel M. Whole-mount in situ hybridization detection of mRNA in GFP-marked Drosophila imaginal disc mosaic clones. Fly (Austin). 2008;2:323-5 pubmed
    ..The methodology described is technically manageable, robust, rapid, relatively inexpensive and of interest to many Drosophila researchers. ..
  2. 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...
  3. 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...
  4. 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...
  5. 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. ..
  6. 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...
  7. 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...
  8. 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 ..
  9. 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
    ..axons to 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...

More Information


  1. 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 ..
  2. 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...
  3. 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...
  4. 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...
  5. 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...
  6. 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...
  7. 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. ..
  8. 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
    ..Loss of netrinA inhibits the breakdown of cell-cell junctions, leading to eversion failure...
  9. 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...
  10. 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. ..
  11. 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 ..
  12. 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. ..
  13. Garbe D, Bashaw G. Independent functions of Slit-Robo repulsion and Netrin-Frazzled attraction regulate axon crossing at the midline in Drosophila. J Neurosci. 2007;27:3584-92 pubmed
    Slit and Netrin and their respective neuronal receptors play critical roles in patterning axonal connections in the developing nervous system by regulating the decision of whether or not to cross the midline...
  14. 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)...
  15. 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 ..
  16. 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...
  17. 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...
  18. 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...
  19. Mauss A, Tripodi M, Evers J, Landgraf M. Midline signalling systems direct the formation of a neural map by dendritic targeting in the Drosophila motor system. PLoS Biol. 2009;7:e1000200 pubmed publisher
    ..We show that the midline signalling systems Slit/Robo and Netrin/Frazzled are the main molecular mechanisms that underlie dendritic targeting with respect to the midline...
  20. 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 ..
  21. 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...
  22. 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. ..
  23. Blader -. Oh, for some simple guidance. Trends Genet. 2000;16:486 pubmed
  24. 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 ..
  25. 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. ..
  26. 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
  27. Giger R, Kolodkin A. Frazzled precision guides axons. Nature. 2000;406:841, 843 pubmed
  28. 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
  29. 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. ..
  30. 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...
  31. 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. ..
  32. 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 ..
  33. Drescher U. Netrins find their receptor. Nature. 1996;384:416-7 pubmed
  34. 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...
  35. 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...
  36. Jordan K, Craver K, Magwire M, Cubilla C, Mackay T, Anholt R. Genome-wide association for sensitivity to chronic oxidative stress in Drosophila melanogaster. PLoS ONE. 2012;7:e38722 pubmed publisher
    ..Many of these genes have human orthologs, highlighting the utility of genome-wide association in Drosophila for studying complex human disease. ..
  37. 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 ..
  38. 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...
  39. Terman J, Kolodkin A. Attracted or repelled? Look within. Neuron. 1999;23:193-5 pubmed
  40. 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. ..
  41. Flannery E, VanZomeren Dohm A, Beach P, Holland W, Duman Scheel M. Induction of cellular growth by the axon guidance regulators netrin A and semaphorin-1a. Dev Neurobiol. 2010;70:473-84 pubmed publisher
    ..In this investigation, the impacts of Netrin A (NetA) and Semaphorin-1a (Sema1a) signaling on cellular growth are examined during wing development...
  42. 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...
  43. 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...
  44. 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. ..
  45. 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...
  46. 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...
  47. 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. ..
  48. 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...
  49. 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. ..
  50. 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...
  51. 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...
  52. 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
  53. Long H, Yoshikawa S, Thomas J. Equivalent Activities of Repulsive Axon Guidance Receptors. J Neurosci. 2016;36:1140-50 pubmed publisher
    ..We went on to show that this common pathway involves Trio, a guanine nucleotide exchange factor known to promote cytoskeletal remodeling. ..
  54. Suryamohan K, Hanson C, Andrews E, Sinha S, SCHEEL M, Halfon M. Redeployment of a conserved gene regulatory network during Aedes aegypti development. Dev Biol. 2016;416:402-13 pubmed publisher
    ..system, including the master regulator single minded and downstream genes including short gastrulation, Star, and NetrinA. In contrast to Drosophila, we find that midline expression of these genes is either absent or severely ..
  55. 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 ..
  56. 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. ..
  57. Lloret Llinares M, Pérez Lluch S, Rossell D, Morán T, Ponsa Cobas J, Auer H, et al. dKDM5/LID regulates H3K4me3 dynamics at the transcription-start site (TSS) of actively transcribed developmental genes. Nucleic Acids Res. 2012;40:9493-505 pubmed publisher
    ..These results indicate that, at developmental genes, dKDM5/LID and ASH2 coordinately regulate H3K4me3 at TSS and that this dynamic regulation contributes to transcription. ..
  58. 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 ..
  59. 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...