Gene Symbol: cxcl12a
Description: chemokine (C-X-C motif) ligand 12a (stromal cell-derived factor 1)
Alias: SDF-1, cxcl12, sdf-1a, sdf1a, wu:fa55e10, wu:fc16h12, wu:fj84c02, stromal cell-derived factor 1, chemokine ligand 12, unm t30516, unm_t30516
Species: zebrafish
Products:     cxcl12a

Top Publications

  1. Staton A, Knaut H, Giraldez A. miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration. Nat Genet. 2011;43:204-11 pubmed publisher
    ..Using target protectors, we demonstrate that miR-430-mediated regulation of endogenous sdf1a (also known as cxcl12a) and cxcr7b (i) facilitates dynamic expression of sdf1a by clearing its mRNA from previous expression domains, (..
  2. Valentin G, Haas P, Gilmour D. The chemokine SDF1a coordinates tissue migration through the spatially restricted activation of Cxcr7 and Cxcr4b. Curr Biol. 2007;17:1026-31 pubmed
    ..Here, we present the first mutant in zebrafish SDF1a/CXCL12a and show, surprisingly, that the resultant phenotype is stronger than a null mutation in its cognate receptor, ..
  3. Matsuda M, Chitnis A. Atoh1a expression must be restricted by Notch signaling for effective morphogenesis of the posterior lateral line primordium in zebrafish. Development. 2010;137:3477-87 pubmed publisher
    ..Together, our observations reveal a genetic regulatory network that explains why atoh1a expression must be restricted by Notch signaling for effective morphogenesis of the pLLp. ..
  4. Blaser H, Eisenbeiss S, Neumann M, Reichman Fried M, Thisse B, Thisse C, et al. Transition from non-motile behaviour to directed migration during early PGC development in zebrafish. J Cell Sci. 2005;118:4027-38 pubmed
    ..These distinctive morphological and molecular alterations could represent a general occurrence in similar processes critical for development and disease. ..
  5. Lopez Schier H, Starr C, Kappler J, Kollmar R, Hudspeth A. Directional cell migration establishes the axes of planar polarity in the posterior lateral-line organ of the zebrafish. Dev Cell. 2004;7:401-12 pubmed
    ..We propose that the global orientation of hair cells relative to the body axes is established through an interaction between directional movement by primordial cells and the timing of neuromast maturation. ..
  6. Doitsidou M, Reichman Fried M, Stebler J, Köprunner M, Dörries J, Meyer D, et al. Guidance of primordial germ cell migration by the chemokine SDF-1. Cell. 2002;111:647-59 pubmed
    ..Finally, we show that the PGCs can be attracted toward an ectopic source of the chemokine, strongly suggesting that this molecule provides a key directional cue for the PGCs. ..
  7. Hess I, Boehm T. Intravital imaging of thymopoiesis reveals dynamic lympho-epithelial interactions. Immunity. 2012;36:298-309 pubmed publisher
    ..Thymocyte development appears to be completed in less than 4 days. Our work establishes a versatile model for the in vivo observation and manipulation of thymopoiesis. ..
  8. Glass T, Lund T, Patrinostro X, Tolar J, Bowman T, Zon L, et al. Stromal cell-derived factor-1 and hematopoietic cell homing in an adult zebrafish model of hematopoietic cell transplantation. Blood. 2011;118:766-74 pubmed publisher
  9. 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. ..

More Information


  1. Li Q, Shirabe K, Kuwada J. Chemokine signaling regulates sensory cell migration in zebrafish. Dev Biol. 2004;269:123-36 pubmed
    ..These data demonstrate that SDF-1 signaling mediated via CXCR4 functions as a chemoattractant for the migrating primordium and that chemokine signaling is both necessary and sufficient for directing primordium migration. ..
  2. Gamba L, Cubedo N, Ghysen A, Lutfalla G, Dambly Chaudiere C. Estrogen receptor ESR1 controls cell migration by repressing chemokine receptor CXCR4 in the zebrafish posterior lateral line system. Proc Natl Acad Sci U S A. 2010;107:6358-63 pubmed publisher
    ..Both ESR1 inactivation and overexpression result in aborted migration, confirming the importance of this receptor in the control of SDF1-dependent migration. ..
  3. Boldajipour B, Mahabaleshwar H, Kardash E, Reichman Fried M, Blaser H, Minina S, et al. Control of chemokine-guided cell migration by ligand sequestration. Cell. 2008;132:463-73 pubmed publisher
    ..We demonstrate that the activity of a second SDF-1/CXCL12 receptor, CXCR7, is crucial for proper migration of PGCs toward their targets...
  4. Cha Y, Fujita M, Butler M, Isogai S, Kochhan E, Siekmann A, et al. Chemokine signaling directs trunk lymphatic network formation along the preexisting blood vasculature. Dev Cell. 2012;22:824-36 pubmed publisher
    ..The chemokine receptors Cxcr4a and Cxcr4b are expressed in lymphatic endothelium, whereas chemokine ligands Cxcl12a and Cxcl12b are expressed in adjacent tissues along which the developing lymphatics align...
  5. Zhang Y, Jin H, Li L, Qin F, Wen Z. cMyb regulates hematopoietic stem/progenitor cell mobilization during zebrafish hematopoiesis. Blood. 2011;118:4093-101 pubmed publisher
    ..mutants are at least partly because of adversely elevated levels of chemokine stromal cell-derived factor 1a (Sdf1a)...
  6. David N, Sapede D, Saint Etienne L, Thisse C, Thisse B, Dambly Chaudiere C, et al. Molecular basis of cell migration in the fish lateral line: role of the chemokine receptor CXCR4 and of its ligand, SDF1. Proc Natl Acad Sci U S A. 2002;99:16297-302 pubmed
    ..We conclude that both the formation and the innervation of this system depend on the SDF1-CXCR4 system, which has also been implicated in several migration events in humans, including metastasis formation and lymphocyte homing. ..
  7. Siekmann A, Standley C, Fogarty K, Wolfe S, Lawson N. Chemokine signaling guides regional patterning of the first embryonic artery. Genes Dev. 2009;23:2272-7 pubmed publisher
    ..These studies reveal unexpected endothelial diversity within the aorta that is necessary to facilitate its regional patterning by local cues. ..
  8. Bouzaffour M, Dufourcq P, Lecaudey V, Haas P, Vriz S. Fgf and Sdf-1 pathways interact during zebrafish fin regeneration. PLoS ONE. 2009;4:e5824 pubmed publisher
    ..We further show that, Sdf1a negatively regulates the expression of fgf20a...
  9. Cubedo N, Cerdan E, Sapede D, Rossel M. CXCR4 and CXCR7 cooperate during tangential migration of facial motoneurons. Mol Cell Neurosci. 2009;40:474-84 pubmed
    Migration of facial motoneurons in the zebrafish hindbrain depends on SDF1/CXCL12 signaling. Recent studies demonstrated that SDF1 can bind two chemokine receptors, CXCR4 and CXCR7...
  10. Mizoguchi T, Verkade H, Heath J, Kuroiwa A, Kikuchi Y. Sdf1/Cxcr4 signaling controls the dorsal migration of endodermal cells during zebrafish gastrulation. Development. 2008;135:2521-9 pubmed publisher
    ..Here we show that sdf1a- and sdf1b-expressing mesodermal cells control the movements of the cxcr4a-expressing endodermal cells...
  11. Dambly Chaudiere C, Cubedo N, Ghysen A. Control of cell migration in the development of the posterior lateral line: antagonistic interactions between the chemokine receptors CXCR4 and CXCR7/RDC1. BMC Dev Biol. 2007;7:23 pubmed
    ..of the primordium is driven by the chemokine SDF1 and by its receptor CXCR4, encoded respectively by the genes sdf1a and cxcr4b...
  12. Knaut H, Blader P, Strahle U, Schier A. Assembly of trigeminal sensory ganglia by chemokine signaling. Neuron. 2005;47:653-66 pubmed
    ..Conversely, ectopic sources of the chemokine SDF1a can attract sensory neurons...
  13. Haas P, Gilmour D. Chemokine signaling mediates self-organizing tissue migration in the zebrafish lateral line. Dev Cell. 2006;10:673-80 pubmed
    ..Moreover, a remarkably small number of SDF1a-responsive cells are able to organize an entire cxcr4b mutant primordium to restore migration and organogenesis in ..
  14. Naumann U, Cameroni E, Pruenster M, Mahabaleshwar H, Raz E, Zerwes H, et al. CXCR7 functions as a scavenger for CXCL12 and CXCL11. PLoS ONE. 2010;5:e9175 pubmed publisher
    CXCR7 (RDC1), the recently discovered second receptor for CXCL12, is phylogenetically closely related to chemokine receptors, but fails to couple to G-proteins and to induce typical chemokine receptor mediated cellular responses...
  15. Venkiteswaran G, Lewellis S, Wang J, Reynolds E, Nicholson C, Knaut H. Generation and dynamics of an endogenous, self-generated signaling gradient across a migrating tissue. Cell. 2013;155:674-87 pubmed publisher
    ..The rear of the primordium generates this gradient through continuous sequestration of Sdf1 protein by the alternate Sdf1-receptor Cxcr7. Modeling shows that this is a physically plausible scenario. ..
  16. Donà E, Barry J, Valentin G, Quirin C, Khmelinskii A, Kunze A, et al. Directional tissue migration through a self-generated chemokine gradient. Nature. 2013;503:285-9 pubmed publisher
    ..Here we define the in vivo dynamics of one key guidance molecule, the chemokine Cxcl12a, by applying a fluorescent timer approach to measure ligand-triggered receptor turnover in living animals...
  17. Sapede D, Rossel M, Dambly Chaudiere C, Ghysen A. Role of SDF1 chemokine in the development of lateral line efferent and facial motor neurons. Proc Natl Acad Sci U S A. 2005;102:1714-8 pubmed
    ..We show that the migration of motor neurons of the facial nucleus from rhombomere 4 to 6 is also affected in sdf1a morphants (embryos injected with morpholine-conjugated antisense oligonucleotides)...
  18. Walters K, Green J, Surfus J, Yoo S, Huttenlocher A. Live imaging of neutrophil motility in a zebrafish model of WHIM syndrome. Blood. 2010;116:2803-11 pubmed publisher
    ..The findings suggest that this transgenic zebrafish model of WHIM syndrome may provide a valuable tool to screen for agents that modify CXCR4-SDF1 retention signals. ..
  19. Dufourcq P, Vriz S. The chemokine SDF-1 regulates blastema formation during zebrafish fin regeneration. Dev Genes Evol. 2006;216:635-9 pubmed
    ..We describe the expression pattern of Sdf1a and Sdf1b (the chemokines stromal-cell-derived factor-1a and 1b) and their two receptors Cxcr4a and Cxcr4b during ..
  20. Minina S, Reichman Fried M, Raz E. Control of receptor internalization, signaling level, and precise arrival at the target in guided cell migration. Curr Biol. 2007;17:1164-72 pubmed
  21. Miyasaka N, Knaut H, Yoshihara Y. Cxcl12/Cxcr4 chemokine signaling is required for placode assembly and sensory axon pathfinding in the zebrafish olfactory system. Development. 2007;134:2459-68 pubmed
    ..cxcr4b, encoding a chemokine receptor, is expressed in the migrating olfactory placodal precursors, and cxcl12a (SDF-1a), encoding a ligand for Cxcr4b, is expressed in the abutting anterior neural plate...
  22. Chong S, Nguyet L, Jiang Y, Korzh V. The chemokine Sdf-1 and its receptor Cxcr4 are required for formation of muscle in zebrafish. BMC Dev Biol. 2007;7:54 pubmed
    ..Previous reports emphasized co-operation of Sdf1a and Cxcr4b...
  23. DeVries M, Kelvin A, Xu L, Ran L, Robinson J, Kelvin D. Defining the origins and evolution of the chemokine/chemokine receptor system. J Immunol. 2006;176:401-15 pubmed
  24. Chen J, Zhu R, Li F, Liang Y, Wang C, Qin Y, et al. MicroRNA-126a Directs Lymphangiogenesis Through Interacting With Chemokine and Flt4 Signaling in Zebrafish. Arterioscler Thromb Vasc Biol. 2016;36:2381-2393 pubmed
    ..Bioinformatics analysis and in vivo report assay identified that miR-126a upregulated Cxcl12a by targeting its 5' untranslated region...
  25. Kunwar P, Siekhaus D, Lehmann R. In vivo migration: a germ cell perspective. Annu Rev Cell Dev Biol. 2006;22:237-65 pubmed
    ..We then compare these systems to highlight the emerging principles. Finally, we contrast the migration of germ cells with that of immune and cancer cells to outline the conserved and different mechanisms. ..
  26. Blaser H, Reichman Fried M, Castanon I, Dumstrei K, Marlow F, Kawakami K, et al. Migration of zebrafish primordial germ cells: a role for myosin contraction and cytoplasmic flow. Dev Cell. 2006;11:613-27 pubmed
    ..The biased formation of new protrusions in a particular region of the cell in response to SDF-1 defines the leading edge and the direction of cell migration. ..
  27. McCullagh B, Costello C, Li L, O Connell C, Codd M, Lawrie A, et al. Elevated plasma CXCL12α is associated with a poorer prognosis in pulmonary arterial hypertension. PLoS ONE. 2015;10:e0123709 pubmed publisher
    Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH)...
  28. Paredes Zúñiga S, Morales R, Muñoz Sánchez S, Muñoz Montecinos C, Parada M, Tapia K, et al. CXCL12a/CXCR4b acts to retain neutrophils in caudal hematopoietic tissue and to antagonize recruitment to an injury site in the zebrafish larva. Immunogenetics. 2017;69:341-349 pubmed publisher
    ..Here, we show that zebrafish mutants lacking functional CXCL12a or CXCR4b show disrupted granulopoiesis in the kidney and increased number of circulating neutrophils...
  29. Breau M, Wilson D, Wilkinson D, Xu Q. Chemokine and Fgf signalling act as opposing guidance cues in formation of the lateral line primordium. Development. 2012;139:2246-53 pubmed publisher
    ..These findings reveal a novel chemotactic role for Fgf signalling in which it enables the coalescence of the lateral line primordium from an initial fuzzy pattern into a compact group of migrating cells. ..
  30. Dumstrei K, Mennecke R, Raz E. Signaling pathways controlling primordial germ cell migration in zebrafish. J Cell Sci. 2004;117:4787-95 pubmed
    ..We therefore conclude that Gi-dependent signaling is essential for directional migration, whereas the PI3K pathway is important for the actual motility of PGCs. ..
  31. Meyers J, Planamento J, Ebrom P, Krulewitz N, Wade E, Pownall M. Sulf1 modulates BMP signaling and is required for somite morphogenesis and development of the horizontal myoseptum. Dev Biol. 2013;378:107-21 pubmed publisher
    ..It also leads to decreased sdf1/cxcl12 expression along the mediolateral trunk musculature...
  32. Torraca V, Tulotta C, Snaar Jagalska B, Meijer A. The chemokine receptor CXCR4 promotes granuloma formation by sustaining a mycobacteria-induced angiogenesis programme. Sci Rep. 2017;7:45061 pubmed publisher
    ..Expression of vegfaa was upregulated to a similar extent in cxcr4b mutants and wildtypes, suggesting that the granuloma vascularisation phenotype of cxcr4b mutants is independent of vascular endothelial growth factor. ..
  33. Torraca V, Cui C, Boland R, Bebelman J, van der Sar A, Smit M, et al. The CXCR3-CXCL11 signaling axis mediates macrophage recruitment and dissemination of mycobacterial infection. Dis Model Mech. 2015;8:253-69 pubmed publisher
    ..The demonstration of a conserved CXCR3-CXCL11 signaling axis in zebrafish extends the translational applicability of this model for studying diseases involving the innate immune system. ..
  34. Fernández J, Bubner E, Takeuchi Y, Yoshizaki G, Wang T, Cummins S, et al. Primordial germ cell migration in the yellowtail kingfish (Seriola lalandi) and identification of stromal cell-derived factor 1. Gen Comp Endocrinol. 2015;213:16-23 pubmed publisher
    ..These results provide a platform for further studies into the molecular machinery of PGC migration in yellowtail kingfish, as well as other perciform fish species. ..
  35. Meyen D, Tarbashevich K, Banisch T, Wittwer C, Reichman Fried M, Maugis B, et al. Dynamic filopodia are required for chemokine-dependent intracellular polarization during guided cell migration in vivo. elife. 2015;4: pubmed publisher
    ..migration, we show that filopodia distribution and their dynamics are dictated by the gradient of the chemokine Cxcl12a. By specifically interfering with filopodia formation, we demonstrate for the first time that these protrusions ..
  36. Huising M, van der Meulen T, Flik G, Verburg van Kemenade B. Three novel carp CXC chemokines are expressed early in ontogeny and at nonimmune sites. Eur J Biochem. 2004;271:4094-106 pubmed publisher
    ..chemokines is an unambiguous orthologue of CXCL14, whereas both others are orthologues of CXCL12, and were named CXCL12a and CXCL12b...
  37. Schlueter P, Sang X, Duan C, Wood A. Insulin-like growth factor receptor 1b is required for zebrafish primordial germ cell migration and survival. Dev Biol. 2007;305:377-87 pubmed
    ..Collectively, these data suggest a novel role for IGF signaling in early germline development, potentially via cross-talk with chemokine signaling pathways. ..
  38. Beis D, Stainier D. In vivo cell biology: following the zebrafish trend. Trends Cell Biol. 2006;16:105-12 pubmed
    ..Although this model system has been predominantly appreciated for its amenability to forward genetics, current advances in imaging technology and an increasing number of transgenic lines are bringing it closer to its full potential. ..
  39. Hortopan G, Dinday M, Baraban S. Spontaneous seizures and altered gene expression in GABA signaling pathways in a mind bomb mutant zebrafish. J Neurosci. 2010;30:13718-28 pubmed publisher
    ..This work may have important implications for neurological and neurodevelopmental disorders associated with mutations in ubiquitin ligase activity. ..
  40. Boldajipour B, Doitsidou M, Tarbashevich K, Laguri C, Yu S, Ries J, et al. Cxcl12 evolution--subfunctionalization of a ligand through altered interaction with the chemokine receptor. Development. 2011;138:2909-14 pubmed publisher
    ..In several vertebrates, PGC migration is guided by Cxcl12, a member of the chemokine superfamily...
  41. Crosier P, Bardsley A, Horsfield J, Krassowska A, Lavallie E, Collins Racie L, et al. In situ hybridization screen in zebrafish for the selection of genes encoding secreted proteins. Dev Dyn. 2001;222:637-44 pubmed
  42. 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
    ..We further reveal an interaction between the Hh and chemokine pathways for axon guidance and show that cxcl12a functions downstream of Shh and depends on Shh for its expression at the optic disc...
  43. Mahabaleshwar H, Tarbashevich K, Nowak M, Brand M, Raz E. ?-arrestin control of late endosomal sorting facilitates decoy receptor function and chemokine gradient formation. Development. 2012;139:2897-902 pubmed publisher
    A crucial regulator of Cxcl12 is the decoy receptor Cxcr7, which controls the level of the chemokine in the tissue. The molecular mechanisms that enable Cxcr7 to function as an efficient molecular sink are not known...
  44. Moissoglu K, Majumdar R, Parent C. Cell migration: sinking in a gradient. Curr Biol. 2014;24:R23-R25 pubmed publisher
    ..How chemoattractant gradients form and persist in complex tissues is a key question in cell migration. Two studies now show that CXCR7 acts as a sink in the migrating zebrafish lateral line primordium to generate SDF1 gradients. ..
  45. Imai F, Yoshizawa A, Matsuzaki A, Oguri E, Araragi M, Nishiwaki Y, et al. Stem-loop binding protein is required for retinal cell proliferation, neurogenesis, and intraretinal axon pathfinding in zebrafish. Dev Biol. 2014;394:94-109 pubmed publisher
    ..Taken together, these data indicate important roles of SLBP in retinal development. ..
  46. Ceci M, Mardones Krsulovic C, Sánchez M, Valdivia L, Allende M. Axon-Schwann cell interactions during peripheral nerve regeneration in zebrafish larvae. Neural Dev. 2014;9:22 pubmed publisher
  47. González Rosa J, Peralta M, Mercader N. Pan-epicardial lineage tracing reveals that epicardium derived cells give rise to myofibroblasts and perivascular cells during zebrafish heart regeneration. Dev Biol. 2012;370:173-86 pubmed publisher
    ..Our results support a model in which the epicardium promotes myocardial regeneration by forming a cellular scaffold, and suggests that it might induce cardiomyocyte proliferation and contribute to neoangiogenesis in a paracrine manner. ..
  48. Venero Galanternik M, Kramer K, Piotrowski T. Heparan Sulfate Proteoglycans Regulate Fgf Signaling and Cell Polarity during Collective Cell Migration. Cell Rep. 2015;: pubmed publisher
    ..The HSPGs themselves are regulated by the Wnt/β-catenin and Fgf pathways and thus are integral components of the regulatory network that coordinates collective cell migration with organ specification and morphogenesis. ..
  49. Xing C, Gong B, Xue Y, Han Y, Wang Y, Meng A, et al. TGFβ1a regulates zebrafish posterior lateral line formation via Smad5 mediated pathway. J Mol Cell Biol. 2015;7:48-61 pubmed publisher
    ..Therefore, TGFβ/Smad5 signaling plays an important role in the zebrafish lateral line formation. ..
  50. Bajoghli B, Aghaallaei N, Hess I, Rode I, Netuschil N, Tay B, et al. Evolution of genetic networks underlying the emergence of thymopoiesis in vertebrates. Cell. 2009;138:186-97 pubmed publisher
    ..Our results provide a framework elucidating the evolution of key features of the adaptive immune system in jawed vertebrates...
  51. Svetic V, Hollway G, Elworthy S, Chipperfield T, Davison C, Adams R, et al. Sdf1a patterns zebrafish melanophores and links the somite and melanophore pattern defects in choker mutants. Development. 2007;134:1011-22 pubmed
    ..In addition, we uncover an aberrant pattern of expression of the gene encoding the chemokine Sdf1a in choker mutant homozygotes that correlates with each aspect of the melanophore pattern defect...
  52. Torregroza I, Holtzinger A, Mendelson K, Liu T, Hla T, Evans T. Regulation of a vascular plexus by gata4 is mediated in zebrafish through the chemokine sdf1a. PLoS ONE. 2012;7:e46844 pubmed publisher
    ..We also found abnormal patterns and levels for the chemokine sdf1a in gata4 morphants, which was found to be functionally relevant, since the embryos also show defects in ..
  53. Gross Thebing T, Paksa A, Raz E. Simultaneous high-resolution detection of multiple transcripts combined with localization of proteins in whole-mount embryos. BMC Biol. 2014;12:55 pubmed publisher
    ..Such a protocol would contribute to biomedical research and clinical diagnostics by providing information regarding the three-dimensional expression pattern of clinical markers. ..