has2

Summary

Gene Symbol: has2
Description: hyaluronan synthase 2
Alias: DG42, hyaluronan synthase 2
Species: zebrafish

Top Publications

  1. Bakkers J, Kramer C, Pothof J, Quaedvlieg N, Spaink H, Hammerschmidt M. Has2 is required upstream of Rac1 to govern dorsal migration of lateral cells during zebrafish gastrulation. Development. 2004;131:525-37 pubmed
    ..Here, we analyze the roles of zebrafish Has2 in normal development...
  2. Smith K, Chocron S, von der Hardt S, de Pater E, Soufan A, Bussmann J, et al. Rotation and asymmetric development of the zebrafish heart requires directed migration of cardiac progenitor cells. Dev Cell. 2008;14:287-97 pubmed publisher
    ..The leftward displacement and rotation of the tube requires hyaluronan synthase 2 expression within the CPCs...
  3. 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. ..
  4. Miyasaka K, Kida Y, Banjo T, Ueki Y, Nagayama K, Matsumoto T, et al. Heartbeat regulates cardiogenesis by suppressing retinoic acid signaling via expression of miR-143. Mech Dev. 2011;128:18-28 pubmed publisher
    ..Our data uncover a novel epigenetic link between heartbeat and cardiac development, with miR-143 as an essential component of the mechanotransduction cascade. ..
  5. Banjo T, Grajcarek J, Yoshino D, Osada H, Miyasaka K, Kida Y, et al. Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21. Nat Commun. 2013;4:1978 pubmed publisher
    ..We conclude that miR-21 is a central component of a flow-controlled mechanotransduction system in a physicogenetic regulatory loop. ..
  6. 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
    ..data with predicted miR-23 target sites combined with in vivo testing, we identified hyaluronic acid synthase 2 (Has2), Icat, and Tmem2 as novel direct targets of miR-23...
  7. Kim Y, Kim M, Koo T, Kim J, Koun S, Ham H, et al. Histone deacetylase is required for the activation of Wnt/?-catenin signaling crucial for heart valve formation in zebrafish embryos. Biochem Biophys Res Commun. 2012;423:140-6 pubmed publisher
    ..Taken together, our results demonstrated that HDAC activity plays a pivotal role in vertebrate heart tube formation by activating Wnt/?-catenin signaling which induces bmp4 expression in AVC myocardial cells. ..
  8. Hurlstone A, Haramis A, Wienholds E, Begthel H, Korving J, Van Eeden F, et al. The Wnt/beta-catenin pathway regulates cardiac valve formation. Nature. 2003;425:633-7 pubmed
    ..Our findings identify a novel role for Wnt/beta-catenin signalling in determining endocardial cell fate. ..
  9. von der Hardt S, Bakkers J, Inbal A, Carvalho L, Solnica Krezel L, Heisenberg C, et al. The Bmp gradient of the zebrafish gastrula guides migrating lateral cells by regulating cell-cell adhesion. Curr Biol. 2007;17:475-87 pubmed

More Information

Publications43

  1. Kim J, Kim H, Koun S, Ham H, Kim M, Rhee M, et al. Zebrafish Crip2 plays a critical role in atrioventricular valve development by downregulating the expression of ECM genes in the endocardial cushion. Mol Cells. 2014;37:406-11 pubmed publisher
    ..In the AVC of Crip2-deficient embryos, the expression of both versican a and hyaluronan synthase 2 (has2) was highly upregulated, but the expression of bone morphogenetic protein 4 (bmp4) and T-box 2b (..
  2. Rost M, Sumanas S. Hyaluronic acid receptor Stabilin-2 regulates Erk phosphorylation and arterial--venous differentiation in zebrafish. PLoS ONE. 2014;9:e88614 pubmed publisher
    ..Simultaneous knockdown of Stabilin-2 and Has2, an HA synthetase, results in a synergistic effect, arguing that HA and Stab2 interact during vasculature formation...
  3. Yin A, Korzh S, Winata C, Korzh V, Gong Z. Wnt signaling is required for early development of zebrafish swimbladder. PLoS ONE. 2011;6:e18431 pubmed publisher
    ..analysis of zebrafish swimbladder development, we first identified, by whole-mount in situ hybridization (WISH), has2 as a mesenchymal marker, sox2 as the earliest epithelial marker, as well as hprt1l and elovl1a as the earliest ..
  4. Chen I, Wang H, Hsieh Y, Huang W, Yeh H, Chuang Y. PRSS23 is essential for the Snail-dependent endothelial-to-mesenchymal transition during valvulogenesis in zebrafish. Cardiovasc Res. 2013;97:443-53 pubmed publisher
    ..We demonstrated for the first time that the initiation of EndoMT in valvulogenesis depends on PRSS23-Snail signalling and that the functional role of PRSS23 during AV valve formation is evolutionarily conserved. ..
  5. Xu J, Zhang R, Zhang T, Zhao G, Huang Y, Wang H, et al. Copper impairs zebrafish swimbladder development by down-regulating Wnt signaling. Aquat Toxicol. 2017;192:155-164 pubmed publisher
  6. Bonetti M, Paardekooper Overman J, Tessadori F, Noël E, Bakkers J, den Hertog J. Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish. Development. 2014;141:1961-70 pubmed publisher
    ..These results suggest that NS and LS Shp2 variant-mediated hyperactivation of MAPK signaling leads to impaired cilia function in Kupffer's vesicle, causing left-right asymmetry defects and defective early cardiac development. ..
  7. 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
    ..In the mutant, the expressions of the atrioventricular canal marker genes, such as tbx2b, hyaluronan synthase 2 (has2), notch1b and bmp4, are changed...
  8. 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
  9. Smith K, Noël E, Thurlings I, Rehmann H, Chocron S, Bakkers J. Bmp and nodal independently regulate lefty1 expression to maintain unilateral nodal activity during left-right axis specification in zebrafish. PLoS Genet. 2011;7:e1002289 pubmed publisher
    ..When nodal flow has been established and Nodal activity is apparent, both Nodal and Bmp independently are required for lefty1 expression to assure unilateral Nodal activation and correct LR patterning. ..
  10. McCarthy N, Sidik A, Bertrand J, Eberhart J. An Fgf-Shh signaling hierarchy regulates early specification of the zebrafish skull. Dev Biol. 2016;415:261-277 pubmed publisher
    ..The expression of hyaluron synthetase 2 (has2) in the cephalic mesoderm requires Fgf signaling and Has2 function, in turn, is required for postchordal ..
  11. Patra C, Diehl F, Ferrazzi F, van Amerongen M, Novoyatleva T, Schaefer L, et al. Nephronectin regulates atrioventricular canal differentiation via Bmp4-Has2 signaling in zebrafish. Development. 2011;138:4499-509 pubmed publisher
    ..bmp4) is expanded and endocardial cells along the extended tube-like structure exhibit characteristics of AV cells (has2, notch1b and Alcam expression, cuboidal cell shape)...
  12. 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 development of ..
  13. Missinato M, Tobita K, Romano N, Carroll J, Tsang M. Extracellular component hyaluronic acid and its receptor Hmmr are required for epicardial EMT during heart regeneration. Cardiovasc Res. 2015;107:487-98 pubmed publisher
    ..HA and Hmmr are required for activated epicardial cell EMT and migration involving the FAK/Src pathway for proper heart regeneration. ..
  14. Liang J, Gui Y, Wang W, Gao S, Li J, Song H. Elevated glucose induces congenital heart defects by altering the expression of tbx5, tbx20, and has2 in developing zebrafish embryos. Birth Defects Res A Clin Mol Teratol. 2010;88:480-6 pubmed publisher
    ..Moreover, the expression patterns of tbx5, tbx20, and has2 were altered in the defective hearts...
  15. Tawk M, Araya C, Lyons D, Reugels A, Girdler G, Bayley P, et al. A mirror-symmetric cell division that orchestrates neuroepithelial morphogenesis. Nature. 2007;446:797-800 pubmed
  16. Khatib A, Lahlil R, Hagedorn M, Delomenie C, Christophe O, Denis C, et al. Biological outcome and mapping of total factor cascades in response to HIF induction during regenerative angiogenesis. Oncotarget. 2016;7:12102-20 pubmed publisher
    ..Taken together, this study revealed the impact of HIF induction on regenerative angiogenesis and provided a framework to develop a gene network leading to regenerative process during HIF expression. ..
  17. Steed E, Faggianelli N, Roth S, Ramspacher C, Concordet J, Vermot J. klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis. Nat Commun. 2016;7:11646 pubmed publisher
  18. 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
    ..Interestingly, hyaluronan synthase 2 (has2), a known downstream target of Tbx2 and producer of hyaluronan (HA) - a major ECM component of the ..
  19. Semino C, Allende M. Chitin oligosaccharides as candidate patterning agents in zebrafish embryogenesis. Int J Dev Biol. 2000;44:183-93 pubmed
    ..Transcripts are detected from late blastula stage, during gastrulation, and move as an anterior-posterior wave of expression in adaxial mesoderm during somitogenesis. ..
  20. Kolpa H, Peal D, Lynch S, Giokas A, Ghatak S, Misra S, et al. miR-21 represses Pdcd4 during cardiac valvulogenesis. Development. 2013;140:2172-80 pubmed publisher
    ..PDCD4 knockdown alone was sufficient to enhance endothelial cell migration. These results demonstrate that miR-21 plays a necessary role in cardiac valvulogenesis, in large part due to an obligatory downregulation of PDCD4. ..
  21. Huang H, Jin T, He J, Ding Q, Xu D, Wang L, et al. Progesterone and adipoQ receptor 11 links ras signaling to cardiac development in zebrafish. Arterioscler Thromb Vasc Biol. 2012;32:2158-70 pubmed publisher
    ..This study not only provides in vivo evidence that PAQR11 plays a critical role in heart morphogenesis but also pinpoints the importance of compartmentalized Ras signaling during development. ..
  22. 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. ..
  23. 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
    ..mutant identified an expansion of expression of known myocardial and endocardial AVC markers, including bmp4 and has2. By contrast, a reduction in the expression of spp1, a marker of the maturing valvular primordia, was observed, ..
  24. Capon S, Baillie G, Bower N, da Silva J, Paterson S, Hogan B, et al. Utilising polymorphisms to achieve allele-specific genome editing in zebrafish. Biol Open. 2017;6:125-131 pubmed publisher
    ..These experiments demonstrate that single nucleotide polymorphisms (SNPs) present throughout the genome can be utilised to increase the efficiency of in cis genome editing using CRISPR/Cas9 in the zebrafish model. ..
  25. Shin S, Lee S, Bae J, Jee J, Cha H, Lee Y. Thymosin beta4 regulates cardiac valve formation via endothelial-mesenchymal transformation in zebrafish embryos. Mol Cells. 2014;37:330-6 pubmed publisher
    ..Taken together, our results demonstrate that TB4 plays a pivotal role in cardiac valve formation by increasing EMT.1. ..
  26. Durst R, Sauls K, Peal D, deVlaming A, Toomer K, Leyne M, et al. Mutations in DCHS1 cause mitral valve prolapse. Nature. 2015;525:109-13 pubmed publisher
    ..Understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds potential for therapeutic insights for this very common disease. ..
  27. Govindan J, Tun K, Iovine M. Cx43-Dependent Skeletal Phenotypes Are Mediated by Interactions between the Hapln1a-ECM and Sema3d during Fin Regeneration. PLoS ONE. 2016;11:e0148202 pubmed publisher
    ..Interactions between the ECM and signaling molecules are complex and our study demonstrates the requirement for components of the Hapln1a-ECM for Sema3d signal transduction. ..
  28. Spicer A, McDonald J. Characterization and molecular evolution of a vertebrate hyaluronan synthase gene family. J Biol Chem. 1998;273:1923-32 pubmed
    ..Furthermore, the Has2 and Has3 genes are identical in structure, suggesting that they arose by a gene duplication event early in ..
  29. Yin A, Korzh V, Gong Z. Perturbation of zebrafish swimbladder development by enhancing Wnt signaling in Wif1 morphants. Biochim Biophys Acta. 2012;1823:236-44 pubmed publisher
    ..Our works established the importance of proper level of Wnt signaling for normal development of swimbladder in zebrafish. ..
  30. Li J, Jia W, Zhao Q. Excessive nitrite affects zebrafish valvulogenesis through yielding too much NO signaling. PLoS ONE. 2014;9:e92728 pubmed publisher
    ..Consistently, excessive nitrite diminished expressions of valve progenitor markers including bmp4, has2, vcana and notch1b at 48 hpf...
  31. Ahuja S, Dogra D, Stainier D, Reischauer S. Id4 functions downstream of Bmp signaling to restrict TCF function in endocardial cells during atrioventricular valve development. Dev Biol. 2016;412:71-82 pubmed publisher
    ..We further show that id4 appears to control the number of endocardial cells that contribute to the AV valves by regulating Wnt signaling in the developing AVC endocardium. ..
  32. Peng X, Li G, Wang Y, Zhuang J, Luo R, Chen J, et al. CXXC5 is required for cardiac looping relating to TGF? signaling pathway in zebrafish. Int J Cardiol. 2016;214:246-53 pubmed publisher
    ..5, hand2, and has2. Co-injection of hand2 mRNA with cxxc5 morpholino rescued the cardiac looping detects...
  33. 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. ..
  34. 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. ..