bmp4

Summary

Gene Symbol: bmp4
Description: bone morphogenetic protein 4
Alias: bmp-4, zbmp-4, zgc:100779, bone morphogenetic protein 4, etID309887.17
Species: zebrafish
Products:     bmp4

Top Publications

  1. Chocron S, Verhoeven M, Rentzsch F, Hammerschmidt M, Bakkers J. Zebrafish Bmp4 regulates left-right asymmetry at two distinct developmental time points. Dev Biol. 2007;305:577-88 pubmed
    ..Using morpholino knock down experiments, we identified Bmp4 as the ligand responsible for both phases of BMP signaling...
  2. Lenhart K, Lin S, Titus T, Postlethwait J, Burdine R. Two additional midline barriers function with midline lefty1 expression to maintain asymmetric Nodal signaling during left-right axis specification in zebrafish. Development. 2011;138:4405-10 pubmed publisher
    ..Bmp represses Nodal signaling independently of lefty1 expression and through the activity of a ligand other than Bmp4. The 'anterior barrier' is mediated by lefty2 expression in the left cardiac field and prevents Nodal activation ..
  3. Connors S, Trout J, Ekker M, Mullins M. The role of tolloid/mini fin in dorsoventral pattern formation of the zebrafish embryo. Development. 1999;126:3119-30 pubmed
    ..This extracellular mechanism is amplified by an autoregulatory loop for bmp gene expression. ..
  4. Holloway B, Gomez de la Torre Canny S, Ye Y, Slusarski D, Freisinger C, Dosch R, et al. A novel role for MAPKAPK2 in morphogenesis during zebrafish development. PLoS Genet. 2009;5:e1000413 pubmed publisher
    ..We postulate that a p38 MAPKAPK2 kinase cascade modulates the activity of F-actin at the yolk cell margin circumference allowing the gradual closure of the blastopore as epiboly progresses. ..
  5. Liu X, Xiong C, Jia S, Zhang Y, Chen Y, Wang Q, et al. Araf kinase antagonizes Nodal-Smad2 activity in mesendoderm development by directly phosphorylating the Smad2 linker region. Nat Commun. 2013;4:1728 pubmed publisher
    ..Our findings open avenues for investigating the potential significance of Raf regulation of transforming growth factor ? signalling in versatile biological and pathological processes in the future. ..
  6. Esterberg R, Fritz A. dlx3b/4b are required for the formation of the preplacodal region and otic placode through local modulation of BMP activity. Dev Biol. 2009;325:189-99 pubmed publisher
    ..Morpholino-mediated knockdown of Dlx3b/4b results in loss of cv2 expression in the PPR and a transient increase in Bmp4 activity that lasts throughout early somitogenesis...
  7. Tsang M, Maegawa S, Kiang A, Habas R, Weinberg E, Dawid I. A role for MKP3 in axial patterning of the zebrafish embryo. Development. 2004;131:2769-79 pubmed
    ..Thus, mkp3 encodes a feedback attenuator of the FGF pathway, the expression of which is initiated at an early stage so as to ensure correct FGF signaling levels at the time of axial patterning. ..
  8. 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
  9. Thisse C, Thisse B. Antivin, a novel and divergent member of the TGFbeta superfamily, negatively regulates mesoderm induction. Development. 1999;126:229-40 pubmed
    ..On the basis of its expression and activity, we propose that Antivin normally functions as a competitive inhibitor of Activin to limit mesoderm induction in the early embryo. ..

More Information

Publications67

  1. Bartman T, Walsh E, Wen K, McKane M, Ren J, Alexander J, et al. Early myocardial function affects endocardial cushion development in zebrafish. PLoS Biol. 2004;2:E129 pubmed
  2. Chen J, van Eeden F, Warren K, Chin A, Nusslein Volhard C, Haffter P, et al. Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish. Development. 1997;124:4373-82 pubmed
    The first evident break in left-right symmetry of the primitive zebrafish heart tube is the shift in pattern of BMP4 expression from radially symmetric to left-predominant...
  3. Shimizu T, Bae Y, Muraoka O, Hibi M. Interaction of Wnt and caudal-related genes in zebrafish posterior body formation. Dev Biol. 2005;279:125-41 pubmed
    ..These data indicate that the cdx genes mediate Wnt signaling and play essential roles in the morphogenesis of the posterior body in zebrafish. ..
  4. Martinez Barbera J, Toresson H, Da Rocha S, Krauss S. Cloning and expression of three members of the zebrafish Bmp family: Bmp2a, Bmp2b and Bmp4. Gene. 1997;198:53-9 pubmed
    ..study the evolution of Bmps, we isolated cDNAs for three members of the zebrafish Bmp gene family: Bmp2a, Bmp2b and Bmp4. The deduced amino acid sequences of Bmp2a and Bmp4 consist of 386 and 400 aa, respectively and show high ..
  5. Zuniga E, Rippen M, Alexander C, Schilling T, Crump J. Gremlin 2 regulates distinct roles of BMP and Endothelin 1 signaling in dorsoventral patterning of the facial skeleton. Development. 2011;138:5147-56 pubmed publisher
  6. Lee Y, Cope J, Ackermann G, Goishi K, Armstrong E, Paw B, et al. Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish. Dev Dyn. 2006;235:29-37 pubmed
    ..Taken together, these data demonstrate a novel function for VEGF-Rs in the endocardial endothelium of the developing cardiac valve. ..
  7. Schmid B, Fürthauer M, Connors S, Trout J, Thisse B, Thisse C, et al. Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation. Development. 2000;127:957-67 pubmed
  8. Schilling T, Concordet J, Ingham P. Regulation of left-right asymmetries in the zebrafish by Shh and BMP4. Dev Biol. 1999;210:277-87 pubmed
    ..Misexpression of Bone Morphogenetic Protein (BMP4) on the right side reverses the heart, but visceral organs are unaffected, consistent with a function for BMPs ..
  9. Row R, Kimelman D. Bmp inhibition is necessary for post-gastrulation patterning and morphogenesis of the zebrafish tailbud. Dev Biol. 2009;329:55-63 pubmed publisher
  10. Hammerschmidt M, Serbedzija G, McMahon A. Genetic analysis of dorsoventral pattern formation in the zebrafish: requirement of a BMP-like ventralizing activity and its dorsal repressor. Genes Dev. 1996;10:2452-61 pubmed
    ..We show that at early gastrula stages, dino and swirl mutants display an expanded or reduced Bmp4 expression, respectively...
  11. Zhang Y, Lander A, Nie Q. Computational analysis of BMP gradients in dorsal-ventral patterning of the zebrafish embryo. J Theor Biol. 2007;248:579-89 pubmed
  12. Harvey S, Tümpel S, Dubrulle J, Schier A, Smith J. no tail integrates two modes of mesoderm induction. Development. 2010;137:1127-35 pubmed publisher
    ..At later stages in development ntl is required for notochord formation, and our analysis has also led to the identification of the enhancer required for ntl expression in the developing notochord. ..
  13. Köppen M, Fernández B, Carvalho L, Jacinto A, Heisenberg C. Coordinated cell-shape changes control epithelial movement in zebrafish and Drosophila. Development. 2006;133:2671-81 pubmed
    ..Thus, this study has characterized a conserved mechanism underlying coordinated cell-shape changes during epithelial morphogenesis. ..
  14. Ramel M, Hill C. The ventral to dorsal BMP activity gradient in the early zebrafish embryo is determined by graded expression of BMP ligands. Dev Biol. 2013;378:170-82 pubmed publisher
  15. Fürthauer M, Thisse C, Thisse B. A role for FGF-8 in the dorsoventral patterning of the zebrafish gastrula. Development. 1997;124:4253-64 pubmed
    ..in the ventral part of the embryo as early as blastula stage, suggesting that FGF-8 acts upstream of BMP2 and BMP4. We conclude that FGF-8 is involved in defining dorsoventral identity and is an important organizing factor ..
  16. 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. ..
  17. Garrity D, Childs S, Fishman M. The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome. Development. 2002;129:4635-45 pubmed
    ..However, the syndromic deficiencies of tbx5 mutation are remarkably well retained between fish and mammals. ..
  18. Totong R, Schell T, Lescroart F, Ryckebusch L, Lin Y, Zygmunt T, et al. The novel transmembrane protein Tmem2 is essential for coordination of myocardial and endocardial morphogenesis. Development. 2011;138:4199-205 pubmed publisher
    ..Together, our data reveal that Tmem2 is an essential mediator of myocardium-endocardium coordination during cardiac morphogenesis. ..
  19. 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. ..
  20. Tu C, Yang T, Tsai H. Nkx2.7 and Nkx2.5 function redundantly and are required for cardiac morphogenesis of zebrafish embryos. PLoS ONE. 2009;4:e4249 pubmed publisher
    ..proliferation and defective myocardial differentiation appeared to result from late-stage up-regulation of bmp4, versican, tbx5 and tbx20, which were all expressed normally in hearts at an early stage...
  21. 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. ..
  22. 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
  23. Crotwell P, Mabee P. Gene expression patterns underlying proximal-distal skeletal segmentation in late-stage zebrafish, Danio rerio. Dev Dyn. 2007;236:3111-28 pubmed
    ..Gene co-expression during segmentation (5.5-6.5 mm SL) is similar between tetrapods and zebrafish: bmp2b, bmp4, chordin, and gdf5 in interradial mesenchyme and ZS; bapx1, col2a1, noggin3, and sox9a in chondrocytes...
  24. Esterberg R, Delalande J, Fritz A. Tailbud-derived Bmp4 drives proliferation and inhibits maturation of zebrafish chordamesoderm. Development. 2008;135:3891-901 pubmed publisher
    ..as a transgenic zebrafish line carrying an inducible truncated form of the BMP-type 1 receptor to study the role of Bmp4 outside of the context of DV specification...
  25. 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
    ..We reveal that ndrg4 is required for restricting the expression of versican and bmp4 to the developing atrioventricular canal...
  26. Cao Y, Zhao J, Sun Z, Zhao Z, Postlethwait J, Meng A. fgf17b, a novel member of Fgf family, helps patterning zebrafish embryos. Dev Biol. 2004;271:130-43 pubmed
    ..Like fgf8, activation of fgf17b expression depends on Nodal signaling. ..
  27. Wu M, Ramel M, Howell M, Hill C. SNW1 is a critical regulator of spatial BMP activity, neural plate border formation, and neural crest specification in vertebrate embryos. PLoS Biol. 2011;9:e1000593 pubmed publisher
    ..We conclude that through its ability to regulate a specific domain of BMP activity in the vertebrate embryo, SNW1 is a critical regulator of neural plate border formation and thus neural crest specification...
  28. de Pater E, Clijsters L, Marques S, Lin Y, Garavito Aguilar Z, Yelon D, et al. Distinct phases of cardiomyocyte differentiation regulate growth of the zebrafish heart. Development. 2009;136:1633-41 pubmed publisher
    ..Together, our data support a model in which modified regulation of these distinct phases of cardiomyocyte differentiation has been responsible for the changes in heart size and morphology among vertebrate species. ..
  29. 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. ..
  30. 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
  31. Kawakami A, Nojima Y, Toyoda A, Takahoko M, Satoh M, Tanaka H, et al. The zebrafish-secreted matrix protein you/scube2 is implicated in long-range regulation of hedgehog signaling. Curr Biol. 2005;15:480-8 pubmed
    ..We further show that Bmp activity can be attenuated by the coexpression of Scube2. Our data support the idea that Scube2 can modulate the long-range action of Bmp-dependent signaling in the neural tube and somites. ..
  32. Milan D, Giokas A, Serluca F, Peterson R, Macrae C. Notch1b and neuregulin are required for specification of central cardiac conduction tissue. Development. 2006;133:1125-32 pubmed
  33. Huang H, Zhang B, Hartenstein P, Chen J, Lin S. NXT2 is required for embryonic heart development in zebrafish. BMC Dev Biol. 2005;5:7 pubmed
    ..The defects could be reproduced by morpholino anti-sense oligo knockdown of NXT2. NXT2 has a critical role in maintaining morphogenetic integrity of embryonic heart in vertebrate species. ..
  34. Pittlik S, Domingues S, Meyer A, Begemann G. Expression of zebrafish aldh1a3 (raldh3) and absence of aldh1a1 in teleosts. Gene Expr Patterns. 2008;8:141-7 pubmed publisher
  35. 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
    ..In these embryos, expression of AVC myocardial bmp4 and AVC endocardial notch1b genes was markedly reduced with subsequent failure of EMT in the AVC endocardial cells...
  36. Ulrich F, Krieg M, Schötz E, Link V, Castanon I, Schnabel V, et al. Wnt11 functions in gastrulation by controlling cell cohesion through Rab5c and E-cadherin. Dev Cell. 2005;9:555-64 pubmed
    ..Together, our results suggest that Wnt11 controls tissue morphogenesis by modulating E-cadherin-mediated cell cohesion through Rab5c, a novel mechanism of Wnt signaling in gastrulation. ..
  37. Nojima H, Shimizu T, Kim C, Yabe T, Bae Y, Muraoka O, et al. Genetic evidence for involvement of maternally derived Wnt canonical signaling in dorsal determination in zebrafish. Mech Dev. 2004;121:371-86 pubmed
    ..The tkk locus was mapped to chromosome 16. These data provide genetic evidence that the maternally derived canonical Wnt pathway upstream of beta-catenin is involved in dorsal axis formation in zebrafish. ..
  38. Flores M, Lam E, Crosier K, Crosier P. Osteogenic transcription factor Runx2 is a maternal determinant of dorsoventral patterning in zebrafish. Nat Cell Biol. 2008;10:346-52 pubmed publisher
  39. Dick A, Hild M, Bauer H, Imai Y, Maifeld H, Schier A, et al. Essential role of Bmp7 (snailhouse) and its prodomain in dorsoventral patterning of the zebrafish embryo. Development. 2000;127:343-54 pubmed
    ..mRNA injection studies and double mutant analyses indicate that Bmp2b and Bmp7 closely cooperate and that Bmp2b/Bmp7 signaling is transduced by Smad5 and antagonized by Chordino. ..
  40. Peal D, Burns C, Macrae C, Milan D. Chondroitin sulfate expression is required for cardiac atrioventricular canal formation. Dev Dyn. 2009;238:3103-10 pubmed publisher
  41. Chi N, Shaw R, De Val S, Kang G, Jan L, Black B, et al. Foxn4 directly regulates tbx2b expression and atrioventricular canal formation. Genes Dev. 2008;22:734-9 pubmed publisher
    ..sli/foxn4 is expressed in the AV canal, and its encoded product binds to a highly conserved tbx2 enhancer domain that contains Foxn4- and T-box-binding sites, both necessary to regulate tbx2b expression in the AV canal. ..
  42. Rottbauer W, Wessels G, Dahme T, Just S, Trano N, Hassel D, et al. Cardiac myosin light chain-2: a novel essential component of thick-myofilament assembly and contractility of the heart. Circ Res. 2006;99:323-31 pubmed
    ..Thus, our findings provide the first in vivo evidence that cardiac MLC-2 is required for thick-filament stabilization and contractility in the vertebrate heart. ..
  43. Miller Bertoglio V, Carmany Rampey A, Fürthauer M, Gonzalez E, Thisse C, Thisse B, et al. Maternal and zygotic activity of the zebrafish ogon locus antagonizes BMP signaling. Dev Biol. 1999;214:72-86 pubmed
    ..The results suggest that ogo encodes an as yet unidentified dorsalizing factor that mediates dorsoventral patterning by directly or indirectly antagonizing BMP activity. ..
  44. Patterson S, Bird N, Devoto S. BMP regulation of myogenesis in zebrafish. Dev Dyn. 2010;239:806-17 pubmed publisher
    ..In addition, we show that while BMP overexpression is sufficient to delay myogenic differentiation, inhibition of BMP does not detectably affect this process, suggesting that other factors redundantly inhibit myogenic differentiation. ..
  45. Smith A, Avaron F, Guay D, Padhi B, Akimenko M. Inhibition of BMP signaling during zebrafish fin regeneration disrupts fin growth and scleroblasts differentiation and function. Dev Biol. 2006;299:438-54 pubmed
    ..Here we show that in addition to bmp2b and bmp4 another family member, bmp6, is involved in fin regeneration...
  46. Wang W, Melville D, Montero Balaguer M, Hatzopoulos A, Knapik E. Tfap2a and Foxd3 regulate early steps in the development of the neural crest progenitor population. Dev Biol. 2011;360:173-85 pubmed publisher
  47. Stickney H, Imai Y, Draper B, Moens C, Talbot W. Zebrafish bmp4 functions during late gastrulation to specify ventroposterior cell fates. Dev Biol. 2007;310:71-84 pubmed
    ..homeobox genes vox and vent, which function in parallel to bmp signaling, we identified an insertion mutation in bmp4. We then performed a reverse genetic screen to isolate a null allele of bmp4...
  48. Maegawa S, Varga M, Weinberg E. FGF signaling is required for {beta}-catenin-mediated induction of the zebrafish organizer. Development. 2006;133:3265-76 pubmed
    ..By contrast, when FGF signaling is inhibited, beta-catenin did not induce goosecoid and chordin, repress bmp4 expression or induce a dorsal axis...
  49. French C, Erickson T, French D, Pilgrim D, Waskiewicz A. Gdf6a is required for the initiation of dorsal-ventral retinal patterning and lens development. Dev Biol. 2009;333:37-47 pubmed publisher
    ..In this study, we investigate the functions of two zebrafish Bmps, Gdf6a and Bmp4, during initiation of dorsal retinal identity, and subsequently during lens differentiation...
  50. Alexander C, Zuniga E, Blitz I, Wada N, Le Pabic P, Javidan Y, et al. Combinatorial roles for BMPs and Endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton. Development. 2011;138:5135-46 pubmed publisher
  51. 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
    ..These studies demonstrate that controlling the correct balance of Tbx5 activity is crucial for the specification of the AV boundary and valve formation. ..
  52. Nguyen V, Schmid B, Trout J, Connors S, Ekker M, Mullins M. Ventral and lateral regions of the zebrafish gastrula, including the neural crest progenitors, are established by a bmp2b/swirl pathway of genes. Dev Biol. 1998;199:93-110 pubmed
    ..The dorsalized mutant phenotypes of these genes can be rescued by overexpression of bmp4, bmp2b, an activated BMP type I receptor, and the downstream functioning Smad1 gene...
  53. 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
    ..Together, these results support a model in which CPCs migrate toward a BMP source during development of the linear heart tube, providing a mechanism by which the left-right axis drives asymmetric development of the vertebrate heart. ..
  54. Leung A, Mendenhall E, Kwan T, Liang R, Eckfeldt C, Chen E, et al. Characterization of expanded intermediate cell mass in zebrafish chordin morphant embryos. Dev Biol. 2005;277:235-54 pubmed
    ..b>BMP4 (but not BMP2b or 7) and smad5 mRNA were ectopically expressed in the ChdMO ICM...
  55. Sidi S, Goutel C, Peyrieras N, Rosa F. Maternal induction of ventral fate by zebrafish radar. Proc Natl Acad Sci U S A. 2003;100:3315-20 pubmed
    ..They might further indicate that maternal TGF-betaRdr and WntCa(2+) pathways complementarily specify ventral cell fates, with the former triggering bmps expression and the latter indirectly repressing genes encoding BMP antagonists. ..
  56. Kishimoto Y, Lee K, Zon L, Hammerschmidt M, Schulte Merker S. The molecular nature of zebrafish swirl: BMP2 function is essential during early dorsoventral patterning. Development. 1997;124:4457-66 pubmed
    ..In addition zBMP2 has no maternal role in mesoderm induction. Our analysis shows that swirl/BMP2, unlike mouse BMP2 but like mouse BMP4, is required for early dorsoventral patterning of the zebrafish embryo.
  57. Bauer H, Meier A, Hild M, Stachel S, Economides A, Hazelett D, et al. Follistatin and noggin are excluded from the zebrafish organizer. Dev Biol. 1998;204:488-507 pubmed
    ..They can neuralize ectoderm and dorsalize ventral mesoderm by blocking the ventralizing signals Bmp2 and Bmp4. In the zebrafish, null mutations in the chordin gene, named chordino, lead to a severe reduction of organizer ..
  58. Gritsman K, Zhang J, Cheng S, Heckscher E, Talbot W, Schier A. The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Cell. 1999;97:121-32 pubmed
    ..Expression of the murine EGF-CFC gene cripto rescues oep mutants. These results suggest a conserved role for EGF-CFC proteins as essential extracellular cofactors for Nodal signaling during vertebrate development. ..