Gene Symbol: ntn1a
Description: netrin 1a
Alias: net2, ntn2, zgc:136732, netrin-1, net1a, netrin 2
Species: zebrafish

Top Publications

  1. Wilson B, Ii M, Park K, Suli A, Sorensen L, Larrieu Lahargue F, et al. Netrins promote developmental and therapeutic angiogenesis. Science. 2006;313:640-4 pubmed
    ..We propose that the attractive vascular and neural guidance functions of netrins offer a unique therapeutic potential. ..
  2. Park K, Urness L, Senchuk M, Colvin C, Wythe J, Chien C, et al. Identification of new netrin family members in zebrafish: developmental expression of netrin 2 and netrin 4. Dev Dyn. 2005;234:726-31 pubmed
    ..Here, we have cloned two new zebrafish Netrins, netrin 2 and netrin 4, and present a comparative sequence and expression analysis...
  3. Zhang C, Gao J, Zhang H, Sun L, Peng G. Robo2--slit and Dcc--netrin1 coordinate neuron axonal pathfinding within the embryonic axon tracts. J Neurosci. 2012;32:12589-602 pubmed publisher
    ..These findings demonstrate how Robo2-Slit and Dcc-Netrin coordinate the axonal projection choices of the developing neurons in the vertebrate forebrain. ..
  4. Lim A, Suli A, Yaniv K, Weinstein B, Li D, Chien C. Motoneurons are essential for vascular pathfinding. Development. 2011;138:3847-57 pubmed publisher
    ..These results provide a definitive example of the requirement of axons in endothelial guidance leading to the parallel patterning of nerves and vessels in vivo. ..
  5. Castets M, Coissieux M, Delloye Bourgeois C, Bernard L, Delcros J, Bernet A, et al. Inhibition of endothelial cell apoptosis by netrin-1 during angiogenesis. Dev Cell. 2009;16:614-20 pubmed publisher
    ..Thus, the proapoptotic effect of unbound UNC5B and the survival effect of netrin-1 on endothelial cells finely tune the angiogenic process. ..
  6. Lu X, Le Noble F, Yuan L, Jiang Q, de Lafarge B, Sugiyama D, et al. The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature. 2004;432:179-86 pubmed
    ..Netrin-1 causes endothelial filopodial retraction, but only when UNC5B is present. Thus, UNC5B functions as a repulsive netrin receptor in endothelial cells controlling morphogenesis of the vascular system. ..
  7. Bingham S, Toussaint G, Chandrasekhar A. Neuronal development and migration in zebrafish hindbrain explants. J Neurosci Methods. 2005;149:42-9 pubmed
    ..These results suggest that hindbrain explant culture can be employed effectively in zebrafish to analyze neuronal migration and other dynamic processes using pharmacological and imaging techniques. ..
  8. Suli A, Mortimer N, Shepherd I, Chien C. Netrin/DCC signaling controls contralateral dendrites of octavolateralis efferent neurons. J Neurosci. 2006;26:13328-37 pubmed
    ..This work is the first evidence that Netrin/DCC signaling acts in dendrites in a vertebrate system. ..
  9. Gao J, Zhang C, Yang B, Sun L, Zhang C, Westerfield M, et al. Dcc regulates asymmetric outgrowth of forebrain neurons in zebrafish. PLoS ONE. 2012;7:e36516 pubmed publisher
    ..These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates. ..

More Information


  1. Seth A, Culverwell J, Walkowicz M, Toro S, Rick J, Neuhauss S, et al. belladonna/(Ihx2) is required for neural patterning and midline axon guidance in the zebrafish forebrain. Development. 2006;133:725-35 pubmed
    ..Our analysis reveals new roles for Ihx2 in midline axon guidance, forebrain patterning and eye morphogenesis. ..
  2. Lupo G, Gestri G, O Brien M, Denton R, Chandraratna R, Ley S, et al. Retinoic acid receptor signaling regulates choroid fissure closure through independent mechanisms in the ventral optic cup and periocular mesenchyme. Proc Natl Acad Sci U S A. 2011;108:8698-703 pubmed publisher
    ..Furthermore, the identification of two cohorts of genes implicated in ventral eye morphogenesis may help to elucidate the genetic basis of ocular coloboma in humans. ..
  3. Pittman A, Law M, Chien C. Pathfinding in a large vertebrate axon tract: isotypic interactions guide retinotectal axons at multiple choice points. Development. 2008;135:2865-71 pubmed publisher
    ..We conclude that axon-axon interactions and ligand-receptor signaling have co-equal roles, cooperating to ensure the fidelity of axon guidance in developing vertebrate tracts. ..
  4. Chandrasekhar A, Schauerte H, Haffter P, Kuwada J. The zebrafish detour gene is essential for cranial but not spinal motor neuron induction. Development. 1999;126:2727-37 pubmed
  5. Gaudin A, Hofmeister W, Key B. Chemoattractant axon guidance cues regulate de novo axon trajectories in the embryonic forebrain of zebrafish. Dev Biol. 2012;367:126-39 pubmed publisher
    ..This work provides insight into how integration of multiple guidance signals defines the initial scaffold of axon tracts in the embryonic vertebrate forebrain. ..
  6. Hale L, Fowler D, Eisen J. Netrin signaling breaks the equivalence between two identified zebrafish motoneurons revealing a new role of intermediate targets. PLoS ONE. 2011;6:e25841 pubmed publisher
    ..The data we present reveal that signals encountered during axon pathfinding can cause equivalent neurons to adopt distinct fates. Such signals may be key in diversifying a neuronal population and leading to correct circuit formation. ..
  7. Heisenberg C, Brennan C, Wilson S. Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincident defects in CNS development. Development. 1999;126:2129-40 pubmed
    ..We conclude that aus represents a mutation involving a locus normally required for the regulation of ace expression during embryogenesis. ..
  8. Lauderdale J, Pasquali S, Fazel R, van Eeden F, Schauerte H, Haffter P, et al. Regulation of netrin-1a expression by hedgehog proteins. Mol Cell Neurosci. 1998;11:194-205 pubmed
    ..These data demonstrate that in vertebrates netrin expression is regulated by Hedgehog signaling. ..
  9. Vanderlaan G, Tyurina O, Karlstrom R, Chandrasekhar A. Gli function is essential for motor neuron induction in zebrafish. Dev Biol. 2005;282:550-70 pubmed
    ..Interestingly, the expression of some Hh-regulated genes (ptc1, net1a, gli1) is mostly unaffected in the detour mutant hindbrain, suggesting that other Gli transcriptional activators ..
  10. Chen Z, Lee H, Henle S, Cheever T, Ekker S, Henley J. Primary neuron culture for nerve growth and axon guidance studies in zebrafish (Danio rerio). PLoS ONE. 2013;8:e57539 pubmed publisher
    ..Thus, this primary neuron culture model system may be useful for studies of neuronal development, chemotropic axon guidance, and mechanisms underlying inhibition of neural regeneration in vitro, and complement observations made in vivo. ..
  11. Shimeld S. An amphioxus netrin gene is expressed in midline structures during embryonic and larval development. Dev Genes Evol. 2000;210:337-44 pubmed
  12. Ny A, Autiero M, Carmeliet P. Zebrafish and Xenopus tadpoles: small animal models to study angiogenesis and lymphangiogenesis. Exp Cell Res. 2006;312:684-93 pubmed
    ..The advantages of these two models will be discussed in the present review. ..
  13. Samuel A, Rubinstein A, Azar T, Ben Moshe Livne Z, Kim S, Inbal A. Six3 regulates optic nerve development via multiple mechanisms. Sci Rep. 2016;6:20267 pubmed publisher
    ..Hence, the new zebrafish model for Six3 loss of function furthers our understanding of the mechanisms governing optic nerve development and Six3-mediated eye and forebrain malformations. ..
  14. Wild R, Klems A, Takamiya M, Hayashi Y, Strahle U, Ando K, et al. Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization. Nat Commun. 2017;8:13991 pubmed publisher
    ..Conceptually, our data suggest that spinal cord vascularization proceeds from veins involving two-tiered regulation of neuronal sFlt1 and Vegfaa via a novel sprouting mode. ..
  15. Opitz R, Hitz M, Vandernoot I, Trubiroha A, Abu Khudir R, Samuels M, et al. Functional zebrafish studies based on human genotyping point to netrin-1 as a link between aberrant cardiovascular development and thyroid dysgenesis. Endocrinology. 2015;156:377-88 pubmed publisher
    ..In zebrafish, ntn1a and ntn1b were not expressed in thyroid tissue, but ntn1a was expressed in pharyngeal arch mesenchyme, and ntn1a-..
  16. Kastenhuber E, Kern U, Bonkowsky J, Chien C, Driever W, Schweitzer J. Netrin-DCC, Robo-Slit, and heparan sulfate proteoglycans coordinate lateral positioning of longitudinal dopaminergic diencephalospinal axons. J Neurosci. 2009;29:8914-26 pubmed publisher
    ..Simultaneous integrations of repulsive and attractive long-range cues from the midline act in a concerted manner to define lateral positions of DA longitudinal axon tracts. ..
  17. Ke Z, Kondrichin I, Gong Z, Korzh V. Combined activity of the two Gli2 genes of zebrafish play a major role in Hedgehog signaling during zebrafish neurodevelopment. Mol Cell Neurosci. 2008;37:388-401 pubmed
    ..Gli2b acts in cell proliferation and plays an early role in the hindbrain within a regulatory cascade involving Notch and Ngn1, as well as a role as specific activator in rhombomere 4. ..
  18. Xing L, Son J, Stevenson T, Lillesaar C, Bally Cuif L, Dahl T, et al. A Serotonin Circuit Acts as an Environmental Sensor to Mediate Midline Axon Crossing through EphrinB2. J Neurosci. 2015;35:14794-808 pubmed publisher
    ..Finally, this work demonstrates that the vertebrate CNS can modulate its connectivity in response to the external environment. ..
  19. Guenebeaud C, Goldschneider D, Castets M, Guix C, Chazot G, Delloye Bourgeois C, et al. The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation of DAP kinase. Mol Cell. 2010;40:863-76 pubmed publisher
    ..Thus we show here that, in the absence of netrin-1, recruitment of PP2A to UNC5H2/B allows the activation of DAPk via a PP2A-mediated dephosphorylation and that this mechanism is involved in angiogenesis regulation. ..
  20. Miyake A, Mekata Y, Fujibayashi H, Nakanishi K, Konishi M, Itoh N. Brorin is required for neurogenesis, gliogenesis, and commissural axon guidance in the zebrafish forebrain. PLoS ONE. 2017;12:e0176036 pubmed publisher
    ..The present results suggest that Brorin is a secreted Bmp antagonist predominantly expressed in developing neural tissues and that it plays multiple roles in the development of the zebrafish forebrain. ..
  21. Miyasaka N, Wanner A, Li J, Mack Bucher J, Genoud C, Yoshihara Y, et al. Functional development of the olfactory system in zebrafish. Mech Dev. 2013;130:336-46 pubmed publisher
  22. ROSENBERG A, Isaacman Beck J, Franzini Armstrong C, Granato M. Schwann cells and deleted in colorectal carcinoma direct regenerating motor axons towards their original path. J Neurosci. 2014;34:14668-81 pubmed publisher
    ..Thus, Schwann cell and dcc-mediated guidance are critical early during regeneration to direct growth cones across the transection gap and onto their original axonal trajectory. ..
  23. Tu T, Zhang C, Yan H, Luo Y, Kong R, Wen P, et al. CD146 acts as a novel receptor for netrin-1 in promoting angiogenesis and vascular development. Cell Res. 2015;25:275-87 pubmed publisher
  24. Lakhina V, Marcaccio C, Shao X, Lush M, Jain R, Fujimoto E, et al. Netrin/DCC signaling guides olfactory sensory axons to their correct location in the olfactory bulb. J Neurosci. 2012;32:4440-56 pubmed publisher
    ..These findings implicate Netrins as the only known attractants for olfactory sensory neurons, first drawing OR111-7-expressing axons into the bulb and then into the ventromedially positioned central zone protoglomerulus. ..
  25. Li Q, Shirabe K, Thisse C, Thisse B, Okamoto H, Masai I, et al. Chemokine signaling guides axons within the retina in zebrafish. J Neurosci. 2005;25:1711-7 pubmed
    ..These data suggest that chemokine signaling is both necessary and sufficient for directing retinal growth cones within the retina. ..
  26. Bernhardt R. Cellular and molecular bases of axonal pathfinding during embryogenesis of the fish central nervous system. J Neurobiol. 1999;38:137-60 pubmed
    ..Experimental evidence for the functions of these molecules in the zebrafish nervous system is accumulating. In the future, this analysis is expected to profit greatly from genetic screens that have recently been initiated. ..
  27. Stacher Hörndli C, Chien C. Sonic hedgehog is indirectly required for intraretinal axon pathfinding by regulating chemokine expression in the optic stalk. Development. 2012;139:2604-13 pubmed publisher
    ..Together, our results support a model in which Shh acts in RGC axon pathfinding indirectly by regulating axon guidance cues at the optic disc through patterning of the optic stalk. ..
  28. Hofmeister W, Devine C, Rothnagel J, Key B. Frizzled-3a and slit2 genetically interact to modulate midline axon crossing in the telencephalon. Mech Dev. 2012;129:109-24 pubmed publisher
    ..In the absence of this platform of glia, commissural axons fail to cross the rostral midline of the forebrain. ..
  29. Paulus J, Halloran M. Zebrafish bashful/laminin-alpha 1 mutants exhibit multiple axon guidance defects. Dev Dyn. 2006;235:213-24 pubmed
    ..In contrast to CNS axons, most peripheral axons appear normal in bal mutants. Our results, thus, reveal important and diverse functions for laminin-alpha1 in guiding developing axons in vivo. ..
  30. Liu L, Lin M, Lai Z, Jiang J, Huang Y, Jao L, et al. Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway. J Biomed Sci. 2016;23:59 pubmed publisher
    ..Thsd7a could regulate ISV angiogenesis via Notch-dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development of both neural and vascular systems. ..