Genomes and Genes
Gene Symbol: Ntn1
Description: netrin 1
Alias: AI561871, BC019633, Netrin-1, netrin-1
- van Gils J, Derby M, Fernandes L, Ramkhelawon B, Ray T, Rayner K, et al. The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques. Nat Immunol. 2012;13:136-43 pubmed publisher..Thus, netrin-1 promoted atherosclerosis by retaining macrophages in the artery wall. Our results establish a causative role for negative regulators of leukocyte migration in chronic inflammation. ..
- Cotrufo T, Perez Branguli F, Muhaisen A, Ros O, Andres R, Baeriswyl T, et al. A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones. J Neurosci. 2011;31:14463-80 pubmed publisher..Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis. ..
- Tian X, Xia X, Xiong S, Jiang J, Liu D, Liu J. Netrin-1 overexpression in oxygen-induced retinopathy correlates with breakdown of the blood-retina barrier and retinal neovascularization. Ophthalmologica. 2011;226:37-44 pubmed publisher..Recent research has shown netrin-1 to promote neovascularization. We evaluate the expression of netrin-1 during retinal neovascularization in a murine model of oxygen-induced retinopathy...
- Wang W, Grimmer J, Van De Water T, Lufkin T. Hmx2 and Hmx3 homeobox genes direct development of the murine inner ear and hypothalamus and can be functionally replaced by Drosophila Hmx. Dev Cell. 2004;7:439-53 pubmed
- Przyborski S, Knowles B, Ackerman S. Embryonic phenotype of Unc5h3 mutant mice suggests chemorepulsion during the formation of the rostral cerebellar boundary. Development. 1998;125:41-50 pubmed
- Yamagishi S, Hampel F, Hata K, del Toro D, Schwark M, Kvachnina E, et al. FLRT2 and FLRT3 act as repulsive guidance cues for Unc5-positive neurons. EMBO J. 2011;30:2920-33 pubmed publisher..Hence, the shed FLRT2 and FLRT3 ECDs represent a novel family of chemorepellents for Unc5-positive neurons and FLRT2/Unc5D signalling modulates cortical neuron migration. ..
- Li S, Qiu F, Xu A, Price S, Xiang M. Barhl1 regulates migration and survival of cerebellar granule cells by controlling expression of the neurotrophin-3 gene. J Neurosci. 2004;24:3104-14 pubmed..These results suggest that Barhl1 plays an essential role in the migration and survival of cerebellar granule cells and precerebellar neurons and functionally link Barhl1 to the NT-3 signaling pathway during cerebellar development. ..
- Schwarting G, Raitcheva D, Bless E, Ackerman S, Tobet S. Netrin 1-mediated chemoattraction regulates the migratory pathway of LHRH neurons. Eur J Neurosci. 2004;19:11-20 pubmed..Here we extend these studies to show that cVNN trajectories and LHRH cell migration in netrin 1 (Ntn1) mutant mice are also abnormal...
- Fazeli A, Dickinson S, Hermiston M, Tighe R, Steen R, Small C, et al. Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene. Nature. 1997;386:796-804 pubmed..These observations fail to support a tumour-suppressor function for Dcc, but are consistent with the hypothesis that DCC is a component of a receptor for netrin-1. ..
- PuschelPüschel A. Divergent properties of mouse netrins. Mech Dev. 1999;83:65-75 pubmed
- Finger J, Bronson R, Harris B, Johnson K, Przyborski S, Ackerman S. The netrin 1 receptors Unc5h3 and Dcc are necessary at multiple choice points for the guidance of corticospinal tract axons. J Neurosci. 2002;22:10346-56 pubmed..b>Netrin 1, a bifunctional cue involved in both attracting and repelling axons, is involved in many cell migration and axon ..
- Garel S, Yun K, Grosschedl R, Rubenstein J. The early topography of thalamocortical projections is shifted in Ebf1 and Dlx1/2 mutant mice. Development. 2002;129:5621-34 pubmed..These observations suggest that the topography of thalamocortical projections is not strictly determined by cues located within the neocortex and may be regulated by the relative positioning of thalamic axons inside the basal ganglia. ..
- 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..These functions in axon guidance have implications for the pathogenesis of Down Syndrome. ..
- Goldman J, Ashour M, Magdesian M, Tritsch N, Harris S, Christofi N, et al. Netrin-1 promotes excitatory synaptogenesis between cortical neurons by initiating synapse assembly. J Neurosci. 2013;33:17278-89 pubmed publisher..These findings identify netrin-1 as a synapse-enriched protein that promotes synaptogenesis between mammalian cortical neurons. ..
- Kolk S, Gunput R, Tran T, Van den Heuvel D, Prasad A, Hellemons A, et al. Semaphorin 3F is a bifunctional guidance cue for dopaminergic axons and controls their fasciculation, channeling, rostral growth, and intracortical targeting. J Neurosci. 2009;29:12542-57 pubmed publisher..In all, this study provides a framework for additional dissection of the molecular basis of mdDA pathway development and disease. ..
- Kennedy T, Wang H, Marshall W, Tessier Lavigne M. Axon guidance by diffusible chemoattractants: a gradient of netrin protein in the developing spinal cord. J Neurosci. 2006;26:8866-74 pubmed..The detection of a gradient of netrin-1 protein supports the operation of long-range chemotropic mechanisms in the developing nervous system. ..
- Schwarting G, Kostek C, Bless E, Ahmad N, Tobet S. Deleted in colorectal cancer (DCC) regulates the migration of luteinizing hormone-releasing hormone neurons to the basal forebrain. J Neurosci. 2001;21:911-9 pubmed..Loss of DCC function results in the migration of many LHRH neurons to inappropriate destinations. ..
- Bielle F, Marcos Mondejar P, Leyva Díaz E, Lokmane L, Mire E, Mailhes C, et al. Emergent growth cone responses to combinations of Slit1 and Netrin 1 in thalamocortical axon topography. Curr Biol. 2011;21:1748-55 pubmed publisher..this topography is set in a small hub, the corridor, which contains matching rostrocaudal gradients of Slit1 and Netrin 1. Using in vitro and in vivo experiments, we show that Slit1 is a rostral repellent that positions intermediate ..
- Paradisi A, Maisse C, Bernet A, Coissieux M, Maccarrone M, Scoazec J, et al. NF-kappaB regulates netrin-1 expression and affects the conditional tumor suppressive activity of the netrin-1 receptors. Gastroenterology. 2008;135:1248-57 pubmed publisher..We propose that NF-kappaB activation that occurs in response to inflammation confers a selective advantage for tumor development through NF-kappaB-mediated netrin-1 up-regulation. ..
- Hakanen J, Duprat S, Salminen M. Netrin1 is required for neural and glial precursor migrations into the olfactory bulb. Dev Biol. 2011;355:101-14 pubmed publisherNetrin1 (NTN1) deficiency in mouse brain causes defects in axon guidance and cell migration during embryonic development...
- Strizzi L, Bianco C, Raafat A, Abdallah W, Chang C, Raafat D, et al. Netrin-1 regulates invasion and migration of mouse mammary epithelial cells overexpressing Cripto-1 in vitro and in vivo. J Cell Sci. 2005;118:4633-43 pubmed..Together, these results suggest that regulation of Netrin-1 expression is important in regulating Cripto-1-dependent invasion and migration of mammary epithelial cells. ..
- Wang W, Chan E, Baron S, Van de Water T, Lufkin T. Hmx2 homeobox gene control of murine vestibular morphogenesis. Development. 2001;128:5017-29 pubmed
- Shi M, Guo C, Dai J, Ding Y. DCC is required for the tangential migration of noradrenergic neurons in locus coeruleus of mouse brain. Mol Cell Neurosci. 2008;39:529-38 pubmed publisher..Thus, our findings demonstrate that DCC is a key regulator of tangential migration of LC neurons during the embryonic development. ..
- Strickland P, Shin G, Plump A, Tessier Lavigne M, Hinck L. Slit2 and netrin 1 act synergistically as adhesive cues to generate tubular bi-layers during ductal morphogenesis. Development. 2006;133:823-32 pubmed..and Robo1 yield similar phenotypes, characterized by disorganized end buds (EBs) reminiscent of those present in Ntn1(-/-) glands, suggesting that SLIT2 and NTN1 function in concert during mammary development...
- Graef I, Wang F, Charron F, Chen L, Neilson J, Tessier Lavigne M, et al. Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons. Cell. 2003;113:657-70 pubmed..The precise parsing of signals for elongation turning and survival could allow independent control of these processes during development. ..
- Charron F, Stein E, Jeong J, McMahon A, Tessier Lavigne M. The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell. 2003;113:11-23 pubmed..These results provide evidence that Shh, acting via Smo, is a midline-derived chemoattractant for commissural axons and show that a morphogen can also act as an axonal chemoattractant. ..
- Hammond R, Blaess S, Abeliovich A. Sonic hedgehog is a chemoattractant for midbrain dopaminergic axons. PLoS ONE. 2009;4:e7007 pubmed publisher..Furthermore, Shh signaling is involved in determining the structural diversity of these dopaminergic projections. ..
- Fothergill T, Donahoo A, Douglass A, Zalucki O, Yuan J, Shu T, et al. Netrin-DCC signaling regulates corpus callosum formation through attraction of pioneering axons and by modulating Slit2-mediated repulsion. Cereb Cortex. 2014;24:1138-51 pubmed publisher..These results provide the first evidence for how callosal axons integrate multiple guidance cues to navigate the midline. ..
- Howell D, Morgan W, Jarjour A, Spirou G, Berrebi A, Kennedy T, et al. Molecular guidance cues necessary for axon pathfinding from the ventral cochlear nucleus. J Comp Neurol. 2007;504:533-49 pubmed..Taken together, these data show that a functional netrin-DCC signaling system is required for establishing proper VCN axonal projections in the auditory brainstem. ..
- Barallobre M, Del Rio J, Alcantara S, Borrell V, Aguado F, Ruiz M, et al. Aberrant development of hippocampal circuits and altered neural activity in netrin 1-deficient mice. Development. 2000;127:4797-810 pubmed..Here we have examined the role of netrin 1 in the development of hippocampal connections...
- Wang W, Reeves W, Ramesh G. Netrin-1 increases proliferation and migration of renal proximal tubular epithelial cells via the UNC5B receptor. Am J Physiol Renal Physiol. 2009;296:F723-9 pubmed publisher..Moreover, the increase in cell proliferation, but not migration, was mediated via activation of Akt and ERK pathways. ..
- Srinivasan K, Strickland P, Valdes A, Shin G, Hinck L. Netrin-1/neogenin interaction stabilizes multipotent progenitor cap cells during mammary gland morphogenesis. Dev Cell. 2003;4:371-82 pubmed..Our results suggest that netrin-1 and its receptor neogenin provide an adhesive, rather than a guidance, function during nonneural organogenesis. ..
- Yee K, Simon H, Tessier Lavigne M, O Leary D. Extension of long leading processes and neuronal migration in the mammalian brain directed by the chemoattractant netrin-1. Neuron. 1999;24:607-22 pubmed..Our results demonstrate the attraction of migrating neurons in the mammalian brain by an axon guidance molecule and the chemotactic responsiveness of their leading processes. ..
- Wang H, Copeland N, Gilbert D, Jenkins N, Tessier Lavigne M. Netrin-3, a mouse homolog of human NTN2L, is highly expressed in sensory ganglia and shows differential binding to netrin receptors. J Neurosci. 1999;19:4938-47 pubmed..Thus, like netrin-1, netrin-3 may also function in axon guidance during development but may function predominantly in the development of the peripheral nervous system and may act primarily through netrin receptors other than DCC. ..
- Aherne C, Collins C, Masterson J, Tizzano M, Boyle T, Westrich J, et al. Neuronal guidance molecule netrin-1 attenuates inflammatory cell trafficking during acute experimental colitis. Gut. 2012;61:695-705 pubmed publisher..The present study identifies a previously unrecognised role for netrin-1 in attenuating experimental colitis through limitation of neutrophil trafficking. ..
- Tadagavadi R, Wang W, Ramesh G. Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through UNC5B receptor and protects kidney against ischemia-reperfusion injury. J Immunol. 2010;185:3750-8 pubmed publisher..Our studies demonstrate that netrin-1 acting through UNC5B receptor reduces renal ischemia-reperfusion injury and its associated renal inflammation. ..
- Tuttle R, Nakagawa Y, Johnson J, O Leary D. Defects in thalamocortical axon pathfinding correlate with altered cell domains in Mash-1-deficient mice. Development. 1999;126:1903-16 pubmed..In addition, these findings support the hypothesis that ventral telencephalic neurons and their axons guide TCAs through ventral thalamus and into ventral telencephalon. ..
- Grenz A, Dalton J, Bauerle J, Badulak A, Ridyard D, Gandjeva A, et al. Partial netrin-1 deficiency aggravates acute kidney injury. PLoS ONE. 2011;6:e14812 pubmed publisher..Finally, treatment of Ntn-1(+/-) mice with exogenous netrin-1 restored a normal phenotype during AKI. Taking together, these studies implicate endogenous netrin-1 in attenuating renal inflammation during AKI. ..
- Abraira V, Del Rio T, Tucker A, Slonimsky J, Keirnes H, Goodrich L. Cross-repressive interactions between Lrig3 and netrin 1 shape the architecture of the inner ear. Development. 2008;135:4091-9 pubmed publisher..We show that this phenotype is due to ectopic expression of the axon guidance molecule netrin 1 (Ntn1), which regulates basal lamina integrity in the fusion plate...
- Braisted J, Catalano S, Stimac R, Kennedy T, Tessier Lavigne M, Shatz C, et al. Netrin-1 promotes thalamic axon growth and is required for proper development of the thalamocortical projection. J Neurosci. 2000;20:5792-801 pubmed..These findings demonstrate that netrin-1 promotes the growth of TCAs through the ventral telencephalon and cooperates with other guidance cues to control their pathfinding from dorsal thalamus to cortex. ..
- Alcantara S, Ruiz M, de Castro F, Soriano E, Sotelo C. Netrin 1 acts as an attractive or as a repulsive cue for distinct migrating neurons during the development of the cerebellar system. Development. 2000;127:1359-72 pubmedb>Netrin 1 is a long-range diffusible factor that exerts chemoattractive or chemorepulsive effects on developing axons growing to or away from the neural midline...
- Wang W, Reeves W, Ramesh G. Netrin-1 and kidney injury. I. Netrin-1 protects against ischemia-reperfusion injury of the kidney. Am J Physiol Renal Physiol. 2008;294:F739-47 pubmed publisher..These results suggest that downregulation of netrin-1 in vascular endothelial cells may promote endothelial cell activation and infiltration of leukocytes into the kidney thereby enhancing tubular injury. ..
- Larrivee B, Freitas C, Trombe M, Lv X, Delafarge B, Yuan L, et al. Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis. Genes Dev. 2007;21:2433-47 pubmed..These data show that UNC5B activation inhibits sprouting angiogenesis, thus identifying UNC5B as a potential anti-angiogenic target. ..
- Bonnin A, Torii M, Wang L, Rakic P, Levitt P. Serotonin modulates the response of embryonic thalamocortical axons to netrin-1. Nat Neurosci. 2007;10:588-97 pubmed..These data demonstrate that serotonergic signaling has a previously unrecognized role in the modulation of axonal responsiveness to a classic guidance cue. ..
- Bartoe J, McKenna W, Quan T, Stafford B, Moore J, Xia J, et al. Protein interacting with C-kinase 1/protein kinase Calpha-mediated endocytosis converts netrin-1-mediated repulsion to attraction. J Neurosci. 2006;26:3192-205 pubmed..Together, these data provide a potential mechanism to explain how developing neurons alter their responsiveness to netrin-1 at intermediate choice points as they navigate to their targets. ..
- Lyuksyutova A, Lu C, Milanesio N, King L, Guo N, Wang Y, et al. Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science. 2003;302:1984-8 pubmed..Thus, Wnt-Frizzled signaling guides commissural axons along the anterior-posterior axis of the spinal cord. ..
- Saueressig H, Burrill J, Goulding M. Engrailed-1 and netrin-1 regulate axon pathfinding by association interneurons that project to motor neurons. Development. 1999;126:4201-12 pubmed
- 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. ..
- Matilainen T, Haugas M, Kreidberg J, Salminen M. Analysis of Netrin 1 receptors during inner ear development. Int J Dev Biol. 2007;51:409-13 pubmedb>Netrin 1 plays key roles in axon guidance and neuronal migration during central nervous system (CNS) development. Outside the CNS, Netrin 1 has been shown to be involved in epithelial morphogenesis of various organs...
- Salminen M, Meyer B, Bober E, Gruss P. Netrin 1 is required for semicircular canal formation in the mouse inner ear. Development. 2000;127:13-22 pubmed..We show here that mouse netrin 1, known to be involved in axon guidance and cell migration in the central nervous system, also plays a critical ..
- Metin C, Deléglise D, Serafini T, Kennedy T, Tessier Lavigne M. A role for netrin-1 in the guidance of cortical efferents. Development. 1997;124:5063-74 pubmed
- Zhou C, Pinson K, Pleasure S. Severe defects in dorsal thalamic development in low-density lipoprotein receptor-related protein-6 mutants. J Neurosci. 2004;24:7632-9 pubmed..This study provides compelling in vivo evidence that thalamic development requires normal activity of the LRP6-mediated canonical Wnt signaling pathway. ..
- Burgess R, Jucius T, Ackerman S. Motor axon guidance of the mammalian trochlear and phrenic nerves: dependence on the netrin receptor Unc5c and modifier loci. J Neurosci. 2006;26:5756-66 pubmed..In addition, they demonstrate the importance of modifier genes in vertebrate axonal guidance. ..
- Skarnes W, Moss J, Hurtley S, Beddington R. Capturing genes encoding membrane and secreted proteins important for mouse development. Proc Natl Acad Sci U S A. 1995;92:6592-6 pubmed..Analysis of homozygous mice carrying insertions in LAR and PTP kappa showed that both genes were effectively disrupted, but neither was essential for normal embryonic development. ..
- Deiner M, Kennedy T, Fazeli A, Serafini T, Tessier Lavigne M, Sretavan D. Netrin-1 and DCC mediate axon guidance locally at the optic disc: loss of function leads to optic nerve hypoplasia. Neuron. 1997;19:575-89 pubmed..Thus, netrin-1 through DCC appears to guide RGC axons locally at the optic disc rather than at long range, apparently reflecting the localization of netrin-1 protein to the vicinity of netrin-1-producing cells at the optic disc. ..
- Park K, Crouse D, Lee M, Karnik S, Sorensen L, Murphy K, et al. The axonal attractant Netrin-1 is an angiogenic factor. Proc Natl Acad Sci U S A. 2004;101:16210-5 pubmed..Thus, we demonstrate that Netrin-1 is a secreted neural guidance cue with the unique ability to attract both blood vessels and axons, and suggest that other cues may also function as vascular endothelial growth factors. ..
- Mirakaj V, Gatidou D, Pötzsch C, König K, Rosenberger P. Netrin-1 signaling dampens inflammatory peritonitis. J Immunol. 2011;186:549-55 pubmed publisher..In this article, we report that animals with endogenous repression of netrin-1 (Ntn1(+/-)) demonstrated increased cell count, increased peritoneal cytokine concentration, and pronounced histological ..
- Reeves W, Kwon O, Ramesh G. Netrin-1 and kidney injury. II. Netrin-1 is an early biomarker of acute kidney injury. Am J Physiol Renal Physiol. 2008;294:F731-8 pubmed publisher..Immunohistochemical localization showed that netrin-1 is highly expressed in tubular epithelial cells in transplanted human kidney. We conclude that urinary netrin-1 is a promising early biomarker of renal injury. ..