Gene Symbol: nppa
Description: natriuretic peptide A
Alias: anf, hm:zeh1304, zeh1304, natriuretic peptides A, atrial natriuretic factor, natriuretic peptide precursor A
Species: zebrafish

Top Publications

  1. Smith K, Joziasse I, Chocron S, Van Dinther M, Guryev V, Verhoeven M, et al. Dominant-negative ALK2 allele associates with congenital heart defects. Circulation. 2009;119:3062-9 pubmed publisher
    ..In vivo analysis of zebrafish embryos injected with ALK2 L343P RNA revealed improper atrioventricular canal formation. These data identify the dominant-negative allele ALK2 L343P in a patient with AVS defects. ..
  2. Berdougo E, Coleman H, Lee D, Stainier D, Yelon D. Mutation of weak atrium/atrial myosin heavy chain disrupts atrial function and influences ventricular morphogenesis in zebrafish. Development. 2003;130:6121-9 pubmed
    ..These findings are relevant to our understanding of congenital defects in cardiac chamber morphogenesis. ..
  3. Verhoeven M, Haase C, Christoffels V, Weidinger G, Bakkers J. Wnt signaling regulates atrioventricular canal formation upstream of BMP and Tbx2. Birth Defects Res A Clin Mol Teratol. 2011;91:435-40 pubmed publisher
    ..Furthermore, genetic analysis shows that Wnt/?-catenin signaling is upstream and in a linear pathway with BMP and Tbx2 during AVC specification. ..
  4. Lagendijk A, Goumans M, Burkhard S, Bakkers J. MicroRNA-23 restricts cardiac valve formation by inhibiting Has2 and extracellular hyaluronic acid production. Circ Res. 2011;109:649-57 pubmed publisher
    ..MiR-23 in the embryonic heart is required to restrict endocardial cushion formation by inhibiting Has2 expression and extracellular hyaluronic acid production. ..
  5. Sun X, Hoage T, Bai P, Ding Y, Chen Z, Zhang R, et al. Cardiac hypertrophy involves both myocyte hypertrophy and hyperplasia in anemic zebrafish. PLoS ONE. 2009;4:e6596 pubmed publisher
    ..However, since anemia can induce effects on the heart other than biomechanical, non-anemic zebrafish cardiac hypertrophy models shall be generated and characterized. ..
  6. Qu X, Jia H, Garrity D, Tompkins K, Batts L, Appel B, et al. Ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish. Dev Biol. 2008;317:486-96 pubmed publisher
    ..Together, our studies reveal an essential role of ndrg4 in regulating proliferation and growth of cardiomyocytes, suggesting that ndrg4 may function downstream of tbx5 during heart development and growth. ..
  7. Auman H, Coleman H, Riley H, Olale F, Tsai H, Yelon D. Functional modulation of cardiac form through regionally confined cell shape changes. PLoS Biol. 2007;5:e53 pubmed
    ..Together, these data establish regionally confined cell shape change as a cellular mechanism for chamber emergence and as a link in the relationship between form and function during organ morphogenesis. ..
  8. Gupta V, Gemberling M, Karra R, Rosenfeld G, Evans T, Poss K. An injury-responsive gata4 program shapes the zebrafish cardiac ventricle. Curr Biol. 2013;23:1221-7 pubmed publisher
    ..Our experiments uncover an injury-responsive program that prevents heart failure in juveniles by fortifying the ventricular wall, one that is reiterated in adults to promote regeneration after cardiac damage. ..
  9. Ribeiro I, Kawakami Y, Buscher D, Raya A, Rodriguez Leon J, Morita M, et al. Tbx2 and Tbx3 regulate the dynamics of cell proliferation during heart remodeling. PLoS ONE. 2007;2:e398 pubmed

More Information


  1. Bendig G, Grimmler M, Huttner I, Wessels G, Dahme T, Just S, et al. Integrin-linked kinase, a novel component of the cardiac mechanical stretch sensor, controls contractility in the zebrafish heart. Genes Dev. 2006;20:2361-72 pubmed
    ..lethal zebrafish heart failure mutant main squeeze (msq), we find stretch-responsive genes such as atrial natriuretic factor (anf) and vascular endothelial growth factor (vegf) severely down-regulated...
  2. Vermot J, Forouhar A, Liebling M, Wu D, Plummer D, Gharib M, et al. Reversing blood flows act through klf2a to ensure normal valvulogenesis in the developing heart. PLoS Biol. 2009;7:e1000246 pubmed publisher
  3. Ding Y, Sun X, Huang W, Hoage T, REDFIELD M, Kushwaha S, et al. Haploinsufficiency of target of rapamycin attenuates cardiomyopathies in adult zebrafish. Circ Res. 2011;109:658-69 pubmed publisher
  4. Völkers M, Dolatabadi N, Gude N, Most P, Sussman M, Hassel D. Orai1 deficiency leads to heart failure and skeletal myopathy in zebrafish. J Cell Sci. 2012;125:287-94 pubmed publisher
    ..Our findings identify ORAI1 as an important regulator of cardiac and skeletal muscle function and provide evidence linking ORAI1-mediated calcium signaling to sarcomere integrity and cardiomyocyte function. ..
  5. Huang W, Deng Y, Dong W, Yuan W, Wan Y, Mo X, et al. The effect of excess expression of GFP in a novel heart-specific green fluorescence zebrafish regulated by nppa enhancer at early embryonic development. Mol Biol Rep. 2011;38:793-9 pubmed publisher
    ..zebrafish with a heart-specific expression of green fluorescent protein (GFP)-tagged under control of the nppa enhancer...
  6. Kim K, Antkiewicz D, Yan L, Eliceiri K, Heideman W, Peterson R, et al. Lrrc10 is required for early heart development and function in zebrafish. Dev Biol. 2007;308:494-506 pubmed
    ..Expression of two cardiac genes was deregulated in the morphants including an increase in atrial natriuretic factor, a hallmark for cardiac hypertrophy and failure, and a decrease in cardiac myosin light chain 2, an ..
  7. Becker J, Chatterjee S, Robinson T, Bennett J, Pan kov D, Galindo C, et al. Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development. Development. 2014;141:335-45 pubmed publisher
  8. Scott C, Marsden A, Rebagliati M, Zhang Q, Chamling X, Searby C, et al. Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein. PLoS Genet. 2017;13:e1006936 pubmed publisher
    ..Our work identifies a new function for BBS6 in nuclear-cytoplasmic transport, and provides insight into the disease mechanism underlying the congenital heart defects in McKusick-Kaufman syndrome patients. ..
  9. Ding Y, Sun X, Xu X. TOR-autophagy signaling in adult zebrafish models of cardiomyopathy. Autophagy. 2012;8:142-3 pubmed publisher
    ..Moreover, we detected dynamic TOR-autophagy activities along different stages of cardiomyopathy. This needs to be considered when developing TOR-autophagy-based therapeutics for cardiomyopathy. ..
  10. González Rosa J, Guzmán Martínez G, Marques I, Sánchez Iranzo H, Jiménez Borreguero L, Mercader N. Use of echocardiography reveals reestablishment of ventricular pumping efficiency and partial ventricular wall motion recovery upon ventricular cryoinjury in the zebrafish. PLoS ONE. 2014;9:e115604 pubmed publisher
    ..Functional assessment of heart regeneration by echocardiography allows a deeper understanding of the mechanisms of cardiac regeneration and has the advantage of being easily transferable to other cardiovascular zebrafish disease models. ..
  11. Becker J, Robinson T, Sachidanandan C, Kelly A, Coy S, Peterson R, et al. In vivo natriuretic peptide reporter assay identifies chemical modifiers of hypertrophic cardiomyopathy signalling. Cardiovasc Res. 2012;93:463-70 pubmed publisher
    ..Using the developing zebrafish, we established that the cardiac natriuretic peptide genes (nppa and nppb), known markers of cardiomyocyte hypertrophy and heart failure, were induced in the embryonic heart by ..
  12. Choudhry P, Trede N. DiGeorge syndrome gene tbx1 functions through wnt11r to regulate heart looping and differentiation. PLoS ONE. 2013;8:e58145 pubmed publisher
    ..This is the first study linking tbx1 and non-canonical Wnt signaling and extends our understanding of DGS and heart development. ..
  13. McIntyre J, Edmunds R, Redig M, Mudrock E, Davis J, Incardona J, et al. Confirmation of Stormwater Bioretention Treatment Effectiveness Using Molecular Indicators of Cardiovascular Toxicity in Developing Fish. Environ Sci Technol. 2016;50:1561-9 pubmed publisher
    ..Molecular markers were more sensitive than visible toxicity indicators, and several cardiac-related genes show promise as novel tools for evaluating the effectiveness of evolving stormwater mitigation strategies. ..
  14. Hoshijima K, Hirose S. Expression of endocrine genes in zebrafish larvae in response to environmental salinity. J Endocrinol. 2007;193:481-91 pubmed
  15. Qian Y, Xiao D, Guo X, Chen H, Hao L, Ma X, et al. Multiple gene variations contributed to congenital heart disease via GATA family transcriptional regulation. J Transl Med. 2017;15:69 pubmed publisher
    ..We first validated the E1148 K variant in ZFPM2, which is likely involved in the pathogenesis of CHD via GATA4. Moreover, our results suggest that TES could be a useful tool for discovering sequence variants in CHD patients. ..
  16. Huang L, Gao D, Zhang Y, Wang C, Zuo Z. Exposure to low dose benzo[a]pyrene during early life stages causes symptoms similar to cardiac hypertrophy in adult zebrafish. J Hazard Mater. 2014;276:377-82 pubmed publisher
    ..Therefore, the mechanism of the cardiac hypertrophy caused by BaP exposure during early life stages may be through inducing the expression of CdC42, RhoA and Rac1, together with activating ERK1, 2. ..
  17. Dickover M, Hegarty J, Ly K, Lopez D, Yang H, Zhang R, et al. The atypical Rho GTPase, RhoU, regulates cell-adhesion molecules during cardiac morphogenesis. Dev Biol. 2014;389:182-91 pubmed publisher
    ..Failure to properly form these cell adhesions during cardiac development may lead to structural heart defects and mechanistically account for the cellular events that occur in certain human congenital heart diseases. ..
  18. Deacon D, Nevis K, Cashman T, Zhou Y, Zhao L, Washko D, et al. The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis. Development. 2010;137:1887-96 pubmed publisher
    ..Together, our data uncover the miR-143-add3 genetic pathway as essential for cardiac chamber formation and function through active adjustment of myocardial cell morphology. ..
  19. Maves L, Tyler A, Moens C, Tapscott S. Pbx acts with Hand2 in early myocardial differentiation. Dev Biol. 2009;333:409-18 pubmed publisher
    ..Our findings demonstrate new roles for Pbx proteins in vertebrate cardiac development and also provide new insight into connections between the transcriptional regulation of skeletal and cardiac muscle differentiation programs. ..
  20. Jensen B, Boukens B, Postma A, Gunst Q, van den Hoff M, Moorman A, et al. Identifying the evolutionary building blocks of the cardiac conduction system. PLoS ONE. 2012;7:e44231 pubmed publisher
    ..Our study uncovers the evolutionary building plan of heart and indicates that the building blocks of the conduction system of adult ectothermic vertebrates and embryos of endotherms are similar. ..
  21. Cheng F, Miao L, Wu Q, Gong X, Xiong J, Zhang J. Vinculin b deficiency causes epicardial hyperplasia and coronary vessel disorganization in zebrafish. Development. 2016;143:3522-3531 pubmed
    ..Together, our results reveal a previously unappreciated function of vinculin in epicardium and endocardium and reinforce the notion that well-balanced FAK activity is essential for coronary vessel development. ..
  22. Li M, Hu X, Zhu J, Zhu C, Zhu S, Liu X, et al. Overexpression of miR-19b impairs cardiac development in zebrafish by targeting ctnnb1. Cell Physiol Biochem. 2014;33:1988-2002 pubmed publisher
    ..Our findings suggest that miR-19b regulates laterality development and heart looping in zebrafish embryos by targeting ctnnb1. ..
  23. Li J, Yue Y, Zhao Q. Retinoic Acid Signaling Is Essential for Valvulogenesis by Affecting Endocardial Cushions Formation in Zebrafish Embryos. Zebrafish. 2016;13:9-18 pubmed publisher
    ..Examining the expression patterns of AVC marker genes including bmp4, bmp2b, nppa, notch1b, and has2, we found the morphants displayed abnormal development of endocardial AVC but almost normal ..
  24. Seritrakul P, Gross J. Tet-mediated DNA hydroxymethylation regulates retinal neurogenesis by modulating cell-extrinsic signaling pathways. PLoS Genet. 2017;13:e1006987 pubmed publisher
  25. Kao R, Rurik J, Farr G, Dong X, Majesky M, Maves L. Pbx4 is Required for the Temporal Onset of Zebrafish Myocardial Differentiation. J Dev Biol. 2015;3:93-111 pubmed
    ..In summary, our data show that Pbx4 is required for the proper temporal activation of myocardial differentiation and establish a basis for studying additional roles of Pbx factors in heart development. ..
  26. Scheid L, Mosqueira M, Hein S, Kossack M, Juergensen L, Mueller M, et al. Essential light chain S195 phosphorylation is required for cardiac adaptation under physical stress. Cardiovasc Res. 2016;111:44-55 pubmed publisher
  27. Poon K, Liebling M, Kondrychyn I, Brand T, Korzh V. Development of the cardiac conduction system in zebrafish. Gene Expr Patterns. 2016;21:89-96 pubmed publisher
    ..Fhf2a is represented by three transcripts, one of which is expressed in the developing heart. These transgenics are useful tools for studies of development of the CCS and cardiac disease. ..
  28. Sun Y, Wang Q, Fang Y, Wu C, Lu G, Chen Z. Activation of the Nkx2.5-Calr-p53 signaling pathway by hyperglycemia induces cardiac remodeling and dysfunction in adult zebrafish. Dis Model Mech. 2017;10:1217-1227 pubmed publisher
    ..Hyperglycemia-induced myocardial apoptosis was mediated, at least in part, by activation of the Nkx2.5-Calr-p53 pathway in vivo, resulting in cardiac dysfunction and hyperglycemia-induced cardiomyopathy. ..
  29. Sedletcaia A, Evans T. Heart chamber size in zebrafish is regulated redundantly by duplicated tbx2 genes. Dev Dyn. 2011;240:1548-57 pubmed publisher
    ..Therefore, in zebrafish, two tbx2 genes are functionally redundant for regulating chamber development, while each gene is required independently for development of the AVC. ..
  30. Meder B, Huttner I, Sedaghat Hamedani F, Just S, Dahme T, Frese K, et al. PINCH proteins regulate cardiac contractility by modulating integrin-linked kinase-protein kinase B signaling. Mol Cell Biol. 2011;31:3424-35 pubmed publisher
    ..Inactivation of either PINCH isoform independently leads to instability of ILK, loss of stretch-responsive anf and vegf expression, and progressive heart failure...
  31. Noël E, Verhoeven M, Lagendijk A, Tessadori F, Smith K, Choorapoikayil S, et al. A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality. Nat Commun. 2013;4:2754 pubmed publisher
    ..We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping. ..
  32. Cheng L, Guo X, Yang X, Chong M, Cheng J, Li G, et al. Delta-sarcoglycan is necessary for early heart and muscle development in zebrafish. Biochem Biophys Res Commun. 2006;344:1290-9 pubmed
    ..These data together suggest that delta-sarcoglycan plays an important role in early heart and muscle development. ..
  33. Just S, Hirth S, Berger I, Fishman M, Rottbauer W. The mediator complex subunit Med10 regulates heart valve formation in zebrafish by controlling Tbx2b-mediated Has2 expression and cardiac jelly formation. Biochem Biophys Res Commun. 2016;477:581-588 pubmed publisher
    ..We propose here a rather unique role of Med10 in orchestrating cardiac valve formation by mediating Foxn4 dependent tbx2b transcription, expression of Has2 and subsequently proper development of the cardiac jelly. ..
  34. Frabetti F, Casadei R, Lenzi L, Canaider S, Vitale L, Facchin F, et al. Systematic analysis of mRNA 5' coding sequence incompleteness in Danio rerio: an automated EST-based approach. Biol Direct. 2007;2:34 pubmed
    ..3%) mRNAs with putatively incomplete ORFs at 5' region and, in three example cases selected (selt1a, unc119.2, nppa), the extended coding region at 5' end was cloned by reverse transcription-polymerase chain reaction (RT-PCR)...
  35. Gjini E, Hekking L, Küchler A, Saharinen P, Wienholds E, Post J, et al. Zebrafish Tie-2 shares a redundant role with Tie-1 in heart development and regulates vessel integrity. Dis Model Mech. 2011;4:57-66 pubmed publisher
    ..Our study introduces an additional vertebrate model to study in vivo the function of Tie-2 in development and disease. ..
  36. Spaich S, Will R, Just S, Spaich S, Kuhn C, Frank D, et al. F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box protein that regulates sarcomeric protein turnover and is essential for maintenance of contractile function in vivo. Circ Res. 2012;111:1504-16 pubmed publisher
    ..Fbxl22 promotes the proteasome-dependent degradation of key sarcomeric proteins, such as ?-actinin and filamin C, and is essential for maintenance of normal contractile function in vivo. ..
  37. Li J, Jia W, Zhao Q. Excessive nitrite affects zebrafish valvulogenesis through yielding too much NO signaling. PLoS ONE. 2014;9:e92728 pubmed publisher
    ..Taken together, our results show that excessive nitrite affects early valve leaflet formation by producing too much NO signaling. ..
  38. Takeuchi J, Lou X, Alexander J, Sugizaki H, Delgado Olguin P, Holloway A, et al. Chromatin remodelling complex dosage modulates transcription factor function in heart development. Nat Commun. 2011;2:187 pubmed publisher
  39. Musso G, Tasan M, Mosimann C, Beaver J, Plovie E, Carr L, et al. Novel cardiovascular gene functions revealed via systematic phenotype prediction in zebrafish. Development. 2014;141:224-35 pubmed publisher
    ..Thus, we show that systematic prioritization in zebrafish can accelerate the pace of developmental gene function discovery. ..
  40. Jia H, King I, Chopra S, Wan H, Ni T, Jiang C, et al. Vertebrate heart growth is regulated by functional antagonism between Gridlock and Gata5. Proc Natl Acad Sci U S A. 2007;104:14008-13 pubmed
    ..Hence, our studies suggest that Grl regulates embryonic heart growth via opposing Gata5, at least in part through their protein interactions in modulating gene expression. ..
  41. Chetaille P, Preuss C, Burkhard S, Côté J, Houde C, Castilloux J, et al. Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm. Nat Genet. 2014;46:1245-9 pubmed publisher
    ..Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm. ..
  42. Becker J, Deo R, Werdich A, Panàkovà D, Coy S, Macrae C. Human cardiomyopathy mutations induce myocyte hyperplasia and activate hypertrophic pathways during cardiogenesis in zebrafish. Dis Model Mech. 2011;4:400-10 pubmed publisher
  43. Meder B, Just S, Vogel B, Rudloff J, Gärtner L, Dahme T, et al. JunB-CBFbeta signaling is essential to maintain sarcomeric Z-disc structure and when defective leads to heart failure. J Cell Sci. 2010;123:2613-20 pubmed publisher
  44. Camarata T, Krcmery J, Snyder D, Park S, Topczewski J, Simon H. Pdlim7 (LMP4) regulation of Tbx5 specifies zebrafish heart atrio-ventricular boundary and valve formation. Dev Biol. 2010;337:233-45 pubmed publisher
    ..We show that Pdlim7/Tbx5 interactions affect the expression of Tbx5 target genes nppa and tbx2b at the AV boundary, and their domains of misexpression directly correlate with the identified valve ..
  45. Tong X, Zu Y, Li Z, Li W, Ying L, Yang J, et al. Kctd10 regulates heart morphogenesis by repressing the transcriptional activity of Tbx5a in zebrafish. Nat Commun. 2014;5:3153 pubmed publisher
    ..Our results reveal a new essential factor for cardiac development and suggest that KCTD10 could be considered as a new causative gene of congenital heart disease...
  46. Razaghi B, Steele S, Prykhozhij S, Stoyek M, Hill J, Cooper M, et al. hace1 Influences zebrafish cardiac development via ROS-dependent mechanisms. Dev Dyn. 2018;247:289-303 pubmed publisher
    ..Our study demonstrates that HACE1 is critical in the normal development and proper function of the vertebrate heart via a ROS-dependent mechanism. Developmental Dynamics 247:289-303, 2018. © 2017 Wiley Periodicals, Inc. ..
  47. Parrie L, Renfrew E, Wal A, Mueller R, Garrity D. Zebrafish tbx5 paralogs demonstrate independent essential requirements in cardiac and pectoral fin development. Dev Dyn. 2013;242:485-502 pubmed publisher
    ..Collectively, these data indicate that, despite similar spatio-temporal expression patterns, tbx5a and tbx5b have independent functions in heart and fin development. ..
  48. Smith K, Lagendijk A, Courtney A, Chen H, Paterson S, Hogan B, et al. Transmembrane protein 2 (Tmem2) is required to regionally restrict atrioventricular canal boundary and endocardial cushion development. Development. 2011;138:4193-8 pubmed publisher
    ..Finally, we show that immature AVC expansion in wkm mutants is rescued by depleting Bmp4, indicating that Tmem2 restricts bmp4 expression to delimit the AVC primordium during cardiac development. ..
  49. Yin N, Jin X, He J, Yin Z. Effects of adrenergic agents on the expression of zebrafish (Danio rerio) vitellogenin Ao1. Toxicol Appl Pharmacol. 2009;238:20-6 pubmed publisher
    ..Thus, our present data indicate that the production of teleost VTG in vivo can be regulated not only by estrogenic agents, but by adrenergic signals as well...
  50. Powell R, Bubenshchikova E, Fukuyo Y, Hsu C, Lakiza O, Nomura H, et al. Wtip is required for proepicardial organ specification and cardiac left/right asymmetry in zebrafish. Mol Med Rep. 2016;14:2665-78 pubmed publisher
    ..The presence of cilia in the PE, and localization of Wtip in the basal body of ciliated cells, raises the possibility of cilia-mediated PE signaling in the embryonic heart. ..
  51. Sun Y, Fang Y, Xu X, Lu G, Chen Z. Evidence of an Association between Age-Related Functional Modifications and Pathophysiological Changes in Zebrafish Heart. Gerontology. 2015;61:435-47 pubmed publisher
    ..Both nppa and nppb (cardiac fetal genes for natriuretic factor) expression detected by real-time polymerase chain reaction ..
  52. Shi X, Verma S, Yun J, Brand Arzamendi K, Singh K, Liu X, et al. Effect of empagliflozin on cardiac biomarkers in a zebrafish model of heart failure: clues to the EMPA-REG OUTCOME trial?. Mol Cell Biochem. 2017;433:97-102 pubmed publisher
    ..These findings provide important translational clues to the cardiovascular benefits documented in the EMPA-REG OUTCOME study. ..
  53. Poon K, Tan K, Wei Y, Ng C, Colman A, Korzh V, et al. RNA-binding protein RBM24 is required for sarcomere assembly and heart contractility. Cardiovasc Res. 2012;94:418-27 pubmed publisher
    ..This study uncovers a potential novel pathway to cardiomyopathy through down-regulation of the RBP Rbm24. ..