Gene Symbol: Spry1
Description: sprouty RTK signaling antagonist 1
Alias: sprouty1, spry-1, protein sprouty homolog 1, inhibitor of receptor tyrosine kinases, sprouty homolog 1
Species: mouse
Products:     Spry1

Top Publications

  1. Minowada G, Jarvis L, Chi C, Neubüser A, Sun X, Hacohen N, et al. Vertebrate Sprouty genes are induced by FGF signaling and can cause chondrodysplasia when overexpressed. Development. 1999;126:4465-75 pubmed
  2. Mahoney Rogers A, Zhang J, Shim K. Sprouty1 and Sprouty2 limit both the size of the otic placode and hindbrain Wnt8a by antagonizing FGF signaling. Dev Biol. 2011;353:94-104 pubmed publisher
    ..Here we report that in Spry1, Spry2 compound mutant embryos (Spry1?/?; Spry2?/? embryos), the otic placode is increased in size...
  3. Trokovic N, Trokovic R, Partanen J. Fibroblast growth factor signalling and regional specification of the pharyngeal ectoderm. Int J Dev Biol. 2005;49:797-805 pubmed
    ..Here we demonstrate localized down-regulation of the expression of the FGF responsive gene, Sprouty1 in the epithelium covering the presumptive second branchial arch of hypomorphic Fgfr1 mutants...
  4. Simrick S, Lickert H, Basson M. Sprouty genes are essential for the normal development of epibranchial ganglia in the mouse embryo. Dev Biol. 2011;358:147-55 pubmed publisher
    ..The morphology of the facial, glossopharyngeal and vagus nerves are abnormal in Spry1-/-;Spry2-/- embryos...
  5. Rozen E, Schmidt H, Dolcet X, Basson M, Jain S, Encinas M. Loss of Sprouty1 rescues renal agenesis caused by Ret mutation. J Am Soc Nephrol. 2009;20:255-9 pubmed publisher
    ..signals, which are provided in part by the receptor tyrosine kinase Ret and the putative tumor suppressor Sprouty1, respectively...
  6. Zaremba A, Schmuecker U, Esche H. Sprouty is a cytoplasmic target of adenoviral E1A oncoproteins to regulate the receptor tyrosine kinase signalling pathway. Virol J. 2011;8:192 pubmed publisher
    ..In a yeast two-hybrid screen we have identified Sprouty1 (Spry1) as a target of adenoviral E1A Oncoproteins...
  7. Basson M, Akbulut S, Watson Johnson J, Simon R, Carroll T, Shakya R, et al. Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Dev Cell. 2005;8:229-39 pubmed
    ..Here we report that loss of the receptor tyrosine kinase (RTK) antagonist, Sprouty1 (Spry1), causes defects in kidney development in mice...
  8. Yang X, Harkins L, Zubanova O, Harrington A, Kovalenko D, Nadeau R, et al. Overexpression of Spry1 in chondrocytes causes attenuated FGFR ubiquitination and sustained ERK activation resulting in chondrodysplasia. Dev Biol. 2008;321:64-76 pubmed publisher
    ..Using a conditional transgenic approach in chondrocytes in vivo, the forced expression of Spry1 resulted in neonatal lethality with accompanying skeletal abnormalities resembling thanatophoric dysplasia II, ..
  9. Klein O, Lyons D, Balooch G, Marshall G, Basson M, Peterka M, et al. An FGF signaling loop sustains the generation of differentiated progeny from stem cells in mouse incisors. Development. 2008;135:377-85 pubmed
    ..These data reveal that the generation of differentiated progeny from a particular stem cell population can be differently regulated in the embryo and adult. ..

More Information


  1. Patel N, Sharpe P, Miletich I. Coordination of epithelial branching and salivary gland lumen formation by Wnt and FGF signals. Dev Biol. 2011;358:156-67 pubmed publisher
    ..Altogether, these findings point to a key function of FGF signaling in the maintenance of an undifferentiated state in endbud cells by inhibition of a ductal fate...
  2. Gross I, Bassit B, Benezra M, Licht J. Mammalian sprouty proteins inhibit cell growth and differentiation by preventing ras activation. J Biol Chem. 2001;276:46460-8 pubmed
    ..In this study, we provide a functional characterization of mammalian Sprouty1 and Sprouty2...
  3. Urness L, Paxton C, Wang X, Schoenwolf G, Mansour S. FGF signaling regulates otic placode induction and refinement by controlling both ectodermal target genes and hindbrain Wnt8a. Dev Biol. 2010;340:595-604 pubmed publisher
    ..Collectively, our results suggest that Wnt8a provides the link between FGF-induced formation of the pre-otic field and restriction of the otic placode to ectoderm adjacent to the hindbrain. ..
  4. Reginensi A, Clarkson M, Neirijnck Y, Lu B, Ohyama T, Groves A, et al. SOX9 controls epithelial branching by activating RET effector genes during kidney development. Hum Mol Genet. 2011;20:1143-53 pubmed publisher
    ..shows that SOX8/9 are required downstream of GDNF signalling for the activation of RET effector genes such as Sprouty1 and Etv5...
  5. Hoshi M, Batourina E, Mendelsohn C, Jain S. Novel mechanisms of early upper and lower urinary tract patterning regulated by RetY1015 docking tyrosine in mice. Development. 2012;139:2405-15 pubmed publisher
    ..Our work demonstrates novel inhibitory roles of RetY1015 and provides a possible mechanistic explanation for some of the confounding broad range phenotypes in individuals with CAKUT...
  6. Macia A, Vaquero M, Gou Fabregas M, Castelblanco E, Valdivielso J, Anerillas C, et al. Sprouty1 induces a senescence-associated secretory phenotype by regulating NF?B activity: implications for tumorigenesis. Cell Death Differ. 2014;21:333-43 pubmed publisher
    Genes of the Sprouty family (Spry1-4) are feedback inhibitors of receptor tyrosine kinase (RTK) signaling. As such, they restrain proliferation of many cell types and have been proposed as tumor-suppressor genes...
  7. Basson M, Watson Johnson J, Shakya R, Akbulut S, Hyink D, Costantini F, et al. Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1. Dev Biol. 2006;299:466-77 pubmed
    ..Here we show that the absence of the receptor tyrosine kinase antagonist Sprouty1 (Spry1) results in irregular branching morphogenesis characterized by both increased number and size of ureteric ..
  8. Shim K, Minowada G, Coling D, Martin G. Sprouty2, a mouse deafness gene, regulates cell fate decisions in the auditory sensory epithelium by antagonizing FGF signaling. Dev Cell. 2005;8:553-64 pubmed
    ..Our results provide evidence that antagonism of FGF signaling by SPRY2 is essential for establishing the cytoarchitecture of the organ of Corti and for hearing. ..
  9. Shea K, Xiang W, LaPorta V, Licht J, Keller C, Basson M, et al. Sprouty1 regulates reversible quiescence of a self-renewing adult muscle stem cell pool during regeneration. Cell Stem Cell. 2010;6:117-29 pubmed publisher
    ..We demonstrate that Sprouty1 (Spry1), a receptor tyrosine kinase signaling inhibitor, is expressed in quiescent Pax7(+) satellite cells in ..
  10. Schutzman J, Martin G. Sprouty genes function in suppression of prostate tumorigenesis. Proc Natl Acad Sci U S A. 2012;109:20023-8 pubmed publisher
    ..Here we show they function in prostate tumor suppression in the mouse. Concomitant inactivation of Spry1 and Spry2 in prostate epithelium causes ductal hyperplasia and low-grade prostatic intraepithelial neoplasia (PIN)...
  11. Impagnatiello M, Weitzer S, Gannon G, Compagni A, Cotten M, Christofori G. Mammalian sprouty-1 and -2 are membrane-anchored phosphoprotein inhibitors of growth factor signaling in endothelial cells. J Cell Biol. 2001;152:1087-98 pubmed
    ..The data indicate that mammalian Spry-1 and -2 are membrane-anchored proteins that negatively regulate angiogenesis-associated RTK signaling, possibly in a RTK-specific fashion. ..
  12. Zhang S, Lin Y, Itäranta P, Yagi A, Vainio S. Expression of Sprouty genes 1, 2 and 4 during mouse organogenesis. Mech Dev. 2001;109:367-70 pubmed
    ..In organs such as the semicircular canal, Rathke's pouch, nasal organs, the follicle of vibrissae and teeth, Sprouty1 and Sprouty2 are expressed in the epithelium and Sprouty4 in the mesenchyme or neuronal tissue, while in the lung ..
  13. Choi H, Cho S, Schwartz R, Choi K. Dual effects of Sprouty1 on TCR signaling depending on the differentiation state of the T cell. J Immunol. 2006;176:6034-45 pubmed
    ..In the immune system, the function of Spry is unknown. In this study, we investigated the role of Spry1 in T cell activation...
  14. Michos O, Cebrian C, Hyink D, Grieshammer U, Williams L, D AGATI V, et al. Kidney development in the absence of Gdnf and Spry1 requires Fgf10. PLoS Genet. 2010;6:e1000809 pubmed publisher
    ..We find that in the absence of the negative regulator Spry1, Gdnf, and Ret are no longer required for extensive kidney development...
  15. Lee J, Lee J, Oh Y, Park J, Choi H, Choi C, et al. Recruitment of Sprouty1 to immune synapse regulates T cell receptor signaling. J Immunol. 2009;183:7178-86 pubmed publisher
    ..We previously reported that Sprouty1, a negative regulator of Ras-MAPK pathway of receptor tyrosine kinases, was induced by TCR signal and inhibited ..
  16. Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456:980-4 pubmed publisher
    ..in fibroblasts of the failing heart, augmenting ERK-MAP kinase activity through inhibition of sprouty homologue 1 (Spry1)...
  17. Klein O, Minowada G, Peterkova R, Kangas A, Yu B, Lesot H, et al. Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling. Dev Cell. 2006;11:181-90 pubmed
  18. Chakkalakal J, Jones K, Basson M, Brack A. The aged niche disrupts muscle stem cell quiescence. Nature. 2012;490:355-60 pubmed publisher
    ..We show in mice that relatively dormant aged satellite cells robustly express sprouty 1 (Spry1), an inhibitor of fibroblast growth factor (FGF) signalling...
  19. Lagha M, Kormish J, Rocancourt D, Manceau M, Epstein J, Zaret K, et al. Pax3 regulation of FGF signaling affects the progression of embryonic progenitor cells into the myogenic program. Genes Dev. 2008;22:1828-37 pubmed publisher
    ..Other FGF signaling components, notably Sprouty1, are also regulated by Pax3...
  20. Li D, Sakuma R, Vakili N, Mo R, Puviindran V, Deimling S, et al. Formation of proximal and anterior limb skeleton requires early function of Irx3 and Irx5 and is negatively regulated by Shh signaling. Dev Cell. 2014;29:233-40 pubmed publisher
    ..Our data provide genetic evidence supporting the concept of early specification and progressive determination of anterior limb pattern. ..
  21. Wright K, Mahoney Rogers A, Zhang J, Shim K. Cooperative and independent functions of FGF and Wnt signaling during early inner ear development. BMC Dev Biol. 2015;15:33 pubmed publisher
    ..We previously demonstrated that the Sprouty1 (Spry1) and Sprouty2 (Spry2) genes antagonize FGF signaling during induction of the otic placode...
  22. Lagha M, Sato T, Regnault B, Cumano A, Zuniga A, Licht J, et al. Transcriptome analyses based on genetic screens for Pax3 myogenic targets in the mouse embryo. BMC Genomics. 2010;11:696 pubmed publisher
    ..In the progenitor cell population, Pax7 and also Hdac5 which is a potential repressor of Foxc2, are subject to positive control by Pax3. ..
  23. Purcell P, Jheon A, Vivero M, Rahimi H, Joo A, Klein O. Spry1 and spry2 are essential for development of the temporomandibular joint. J Dent Res. 2012;91:387-93 pubmed publisher
    ..Using in situ hybridization, we show that Spry1 and Spry2 are highly expressed in muscles attached to the TMJ, including the lateral pterygoid and temporalis ..
  24. Balasooriya G, Johnson J, Basson M, Rawlins E. An FGFR1-SPRY2 Signaling Axis Limits Basal Cell Proliferation in the Steady-State Airway Epithelium. Dev Cell. 2016;37:85-97 pubmed publisher
    ..such mechanism has been identified in skeletal muscle in which pro-proliferative FGFR1 signaling is antagonized by SPRY1 to maintain satellite cell quiescence...
  25. Assinder S, Beniamen D, Lovicu F. Cosuppression of Sprouty and Sprouty-related negative regulators of FGF signalling in prostate cancer: a working hypothesis. Biomed Res Int. 2015;2015:827462 pubmed publisher
    ..Contrary to this, our analyses of prostates from 24-week-old Spry1- or Spry2-deficientmice, either hemizygous (+/-) or homozygous (-/-) for the null allele, revealed a significantly ..
  26. Goldman D, Martin G, Tam P. Fate and function of the ventral ectodermal ridge during mouse tail development. Development. 2000;127:2113-23 pubmed
  27. Krawchuk D, Weiner S, Chen Y, Lu B, Costantini F, Behringer R, et al. Twist1 activity thresholds define multiple functions in limb development. Dev Biol. 2010;347:133-46 pubmed publisher
    ..Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity. ..
  28. Sims Lucas S, Cullen McEwen L, Eswarakumar V, Hains D, Kish K, Becknell B, et al. Deletion of Frs2alpha from the ureteric epithelium causes renal hypoplasia. Am J Physiol Renal Physiol. 2009;297:F1208-19 pubmed publisher
    ..Interestingly, Etv4 and Etv5 expression was unaltered in Frs2alpha(UB-/-) mice, as was Sprouty1, an antagonist of Frs2alpha signaling...
  29. Kiefer S, Robbins L, Stumpff K, Lin C, Ma L, Rauchman M. Sall1-dependent signals affect Wnt signaling and ureter tip fate to initiate kidney development. Development. 2010;137:3099-106 pubmed publisher
    ..These studies indicate that Sall1-dependent signals from the metanephric mesenchyme are required to modulate ureteric bud tip Wnt patterning in order to initiate branching. ..
  30. Migeotte I, Grego Bessa J, Anderson K. Rac1 mediates morphogenetic responses to intercellular signals in the gastrulating mouse embryo. Development. 2011;138:3011-20 pubmed publisher
    ..Rac1 also has essential roles in morphogenesis of the posterior notochordal plate (the node) and the midline. ..
  31. Rawson N, Lischka F, Yee K, Peters A, Tucker E, Meechan D, et al. Specific mesenchymal/epithelial induction of olfactory receptor, vomeronasal, and gonadotropin-releasing hormone (GnRH) neurons. Dev Dyn. 2010;239:1723-38 pubmed publisher
  32. Urs S, Henderson T, Le P, Rosen C, Liaw L. Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction. Br J Nutr. 2012;108:1025-33 pubmed publisher
    We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes...
  33. Shaw A, Meissner A, Dowdle J, Crowley D, Magendantz M, Ouyang C, et al. Sprouty-2 regulates oncogenic K-ras in lung development and tumorigenesis. Genes Dev. 2007;21:694-707 pubmed
    ..These findings indicate that in the lung, Sprouty-2 plays a critical role in the regulation of oncogenic K-ras, and implicate counter-regulatory mechanisms in the pathogenesis of Ras-based disease. ..
  34. Joo A, Long R, Cheng Z, Alexander C, Chang W, Klein O. Sprouty2 regulates endochondral bone formation by modulation of RTK and BMP signaling. Bone. 2016;88:170-179 pubmed publisher
    ..that regulate RTK signaling have been identified, including the four members of the Sprouty (Spry) family (Spry1-4). We report that Spry2 plays an important role in regulation of endochondral bone formation...
  35. Yang X, Kilgallen S, Andreeva V, Spicer D, Pinz I, Friesel R. Conditional expression of Spry1 in neural crest causes craniofacial and cardiac defects. BMC Dev Biol. 2010;10:48 pubmed publisher
    ..To gain insight into the role of Spry1 in neural crest development, we analyzed the developmental effects of conditional expression of Spry1 in neural ..
  36. Linton J, Martin G, Reichardt L. The ECM protein nephronectin promotes kidney development via integrin alpha8beta1-mediated stimulation of Gdnf expression. Development. 2007;134:2501-9 pubmed
    ..Our results thus place nephronectin and alpha8beta1 integrin in a pathway that regulates Gdnf expression and is essential for kidney development. ..
  37. Petersen C, Jheon A, Mostowfi P, Charles C, Ching S, Thirumangalathu S, et al. FGF signaling regulates the number of posterior taste papillae by controlling progenitor field size. PLoS Genet. 2011;7:e1002098 pubmed publisher
    ..resulted in duplication of the CVP as a result of an increase in the size of the placode progenitor field, and Spry1(-/-);Spry2(-/-) embryos had multiple CVPs, demonstrating the redundancy of Sprouty genes in regulating the ..
  38. SMITH K, Ohkubo Y, Maragnoli M, Rasin M, Schwartz M, Sestan N, et al. Midline radial glia translocation and corpus callosum formation require FGF signaling. Nat Neurosci. 2006;9:787-97 pubmed
    ..Hence, FGFs have an important role in the transition from radial glia to astrocytes by stimulating somal translocation of radial glial cells. ..
  39. Yun K, Ajima R, Sharma N, Costantini F, Mackem S, Lewandoski M, et al. Non-canonical Wnt5a/Ror2 signaling regulates kidney morphogenesis by controlling intermediate mesoderm extension. Hum Mol Genet. 2014;23:6807-14 pubmed publisher
    ..This work provides the first evidence of a role of Wnt5a/Ror2 signaling in IM extension and offers new insights into the etiology of CAKUT and possible involvement of Wnt5a/Ror2 mutations...
  40. Gobius I, Morcom L, Suárez R, Bunt J, Bukshpun P, Reardon W, et al. Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum. Cell Rep. 2016;17:735-747 pubmed publisher
    ..Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis. ..
  41. Sabatel C, Cornet A, Tabruyn S, Malvaux L, Castermans K, Martial J, et al. Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively regulates angiogenesis. Mol Cancer. 2010;9:231 pubmed publisher
    ..b>Sprouty1 (SPRY1), an inhibitor of the MAPK pathway, might be one of these new genes...
  42. Mekkawy A, Pourgholami M, Morris D. Human Sprouty1 suppresses growth, migration, and invasion in human breast cancer cells. Tumour Biol. 2014;35:5037-48 pubmed publisher
    ..Expression of human Sprouty1 (hSpry1) gene is downregulated in most breast cancer patients, implicating it as an important tumor suppressor ..
  43. Mansour S, Li C, Urness L. Genetic rescue of Muenke syndrome model hearing loss reveals prolonged FGF-dependent plasticity in cochlear supporting cell fates. Genes Dev. 2013;27:2320-31 pubmed publisher
    ..This property might be exploited for the regulation of sensory cell regeneration from support cells. ..
  44. Kuracha M, Siefker E, Licht J, Govindarajan V. Spry1 and Spry2 are necessary for eyelid closure. Dev Biol. 2013;383:227-38 pubmed publisher
    ..Our previous studies have shown that Spry1 and Spry2, through negative modulation of FGF-ERK signaling, allow lens vesicle separation from the overlying ..
  45. Collins S, Waickman A, Basson A, Kupfer A, Licht J, Horton M, et al. Regulation of CD4? and CD8? effector responses by Sprouty-1. PLoS ONE. 2012;7:e49801 pubmed publisher
    ..In this report we identify Sprouty1 as a downstream target of Egr-3...
  46. Eloy Trinquet S, Wang H, Edom Vovard F, Duprez D. Fgf signaling components are associated with muscles and tendons during limb development. Dev Dyn. 2009;238:1195-206 pubmed publisher
    ..We observed that the transcriptional effector of Fgf signaling, Pea3, and the modulators of Fgf signal, Sprouty1 and 2, were expressed in muscles and tendons and that their expression was enhanced at the myotendinous junctions ..
  47. Thomson R, Pellicano F, Iwata T. Fibroblast growth factor receptor 3 kinase domain mutation increases cortical progenitor proliferation via mitogen-activated protein kinase activation. J Neurochem. 2007;100:1565-78 pubmed
    ..We suggest that temporal activation of MAPK is largely responsible for cell proliferation caused by the Fgfr3 mutation during early stages of cortical development. ..
  48. Steinecke A, Gampe C, Zimmer G, Rudolph J, Bolz J. EphA/ephrin A reverse signaling promotes the migration of cortical interneurons from the medial ganglionic eminence. Development. 2014;141:460-71 pubmed publisher
    ..Thus, besides functions in guiding MGE-derived interneurons to the cortex through forward signaling, here we describe a novel role of the ephrins in driving these neurons to their target via reverse signaling. ..
  49. Huang Z, Chen J, Regan J, Maguire C, Tang R, Dong X, et al. Loss of microRNAs in neural crest leads to cardiovascular syndromes resembling human congenital heart defects. Arterioscler Thromb Vasc Biol. 2010;30:2575-86 pubmed publisher
    ..Our results uncovered a central role for Dicer and miRNAs in NCC survival, migration, and patterning in craniofacial and cardiovascular development which, when mutated, lead to congenital neuro-craniofacial-cardiac defects. ..
  50. Chung A, Xu X, Niederreither K, Cooney A. Loss of orphan nuclear receptor GCNF function disrupts forebrain development and the establishment of the isthmic organizer. Dev Biol. 2006;293:13-24 pubmed
    ..Increased cell death may contribute to the loss of midbrain structure in GCNF-/- embryos. These results indicate that GCNF is required for establishment of the isthmic organizer, thereby regulating the midbrain development. ..
  51. Lefevre J, Short K, Lamberton T, Michos O, Graf D, Smyth I, et al. Branching morphogenesis in the developing kidney is governed by rules that pattern the ureteric tree. Development. 2017;144:4377-4385 pubmed publisher
    ..These findings demonstrate that kidney development occurs by way of a highly conserved reiterative pattern of asymmetric bifurcation that is governed by intrinsic and locally operative mechanisms. ..
  52. Jackson A, Kasah S, Mansour S, Morrow B, Basson M. Endoderm-specific deletion of Tbx1 reveals an FGF-independent role for Tbx1 in pharyngeal apparatus morphogenesis. Dev Dyn. 2014;243:1143-51 pubmed publisher
    ..Tbx1 deletion from the pharyngeal endoderm is sufficient to cause caudal pharyngeal arch segmentation defects by FGF-independent effectors that remain to be identified. ..
  53. Rodríguez Mateo C, Torres B, Gutiérrez G, Pintor Toro J. Downregulation of Lnc-Spry1 mediates TGF-β-induced epithelial-mesenchymal transition by transcriptional and posttranscriptional regulatory mechanisms. Cell Death Differ. 2017;24:785-797 pubmed publisher
    ..Here lnc-Spry1 is identified as an immediate-early regulator of EMT that is downregulated by TGF-β...