Gene Symbol: Bmp4
Description: bone morphogenetic protein 4
Alias: Bmp-4, Bmp2b, Bmp2b-1, Bmp2b1, bone morphogenetic protein 4, bone morphogenetic protein 2B
Species: mouse
Products:     Bmp4

Top Publications

  1. Sheth R, Grégoire D, Dumouchel A, Scotti M, Pham J, Nemec S, et al. Decoupling the function of Hox and Shh in developing limb reveals multiple inputs of Hox genes on limb growth. Development. 2013;140:2130-8 pubmed publisher
  2. Hägglund A, Dahl L, Carlsson L. Lhx2 is required for patterning and expansion of a distinct progenitor cell population committed to eye development. PLoS ONE. 2011;6:e23387 pubmed publisher
    ..Thus, we have defined a distinct progenitor cell population in the forebrain committed to eye development and identified genes linked to Lhx2's function in the expansion and patterning of these progenitor cells. ..
  3. Fu J, Jiang M, Mirando A, Yu H, Hsu W. Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation. Proc Natl Acad Sci U S A. 2009;106:18598-603 pubmed publisher
    ..A reciprocal regulation of Wnt and Gpr177 is essential for the patterning of the anterior-posterior axis during mammalian development. ..
  4. Jin Y, Turcotte T, Crocker A, Han X, Yoon J. The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction. Dev Biol. 2011;352:1-13 pubmed publisher
    ..Thus, our study identifies Rspo2 as a mesenchyme-derived factor that plays critical roles in regulating BA1 patterning and morphogenesis through ectodermal-mesenchymal interaction and a novel genetic factor for cleft palate. ..
  5. Fulcoli F, Huynh T, Scambler P, Baldini A. Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner. PLoS ONE. 2009;4:e6049 pubmed publisher
    ..We discovered that Tbx1 binds Smad1 and suppresses the Bmp4/Smad1 signaling...
  6. Gonçalves A, Zeller R. Genetic analysis reveals an unexpected role of BMP7 in initiation of ureteric bud outgrowth in mouse embryos. PLoS ONE. 2011;6:e19370 pubmed publisher
    Genetic analysis in the mouse revealed that GREMLIN1 (GREM1)-mediated antagonism of BMP4 is essential for ureteric epithelial branching as the disruption of ureteric bud outgrowth and renal agenesis in Grem1-deficient embryos is restored ..
  7. Passa O, Tsalavos S, Belyaev N, Petryk A, Potocnik A, Graf D. Compartmentalization of bone morphogenetic proteins and their antagonists in lymphoid progenitors and supporting microenvironments and functional implications. Immunology. 2011;134:349-59 pubmed publisher
    ..b>Bmp4, Bmp7, Gremlin and Twisted gastrulation (Twsg1) are all expressed in the thymus and expression was clearly ..
  8. Song L, Li Y, Wang K, Wang Y, Molotkov A, Gao L, et al. Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion. Development. 2009;136:3161-71 pubmed publisher
    ..We further demonstrate that Msx1 and Msx2 (but not their potential regulator Bmp4) are the downstream targets of the Wnt/beta-catenin signaling pathway during lip formation and fusion...
  9. Lan Y, Jiang R. Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth. Development. 2009;136:1387-96 pubmed publisher
    ..Furthermore, we show that Shh signaling regulates Bmp2, Bmp4 and Fgf10 expression in the developing palatal mesenchyme and that specific inactivation of Smo in the palatal ..

More Information


  1. Lenox L, Shi L, Hegde S, Paulson R. Extramedullary erythropoiesis in the adult liver requires BMP-4/Smad5-dependent signaling. Exp Hematol. 2009;37:549-58 pubmed publisher
    ..Our data indicate that the BMP-4-dependent stress erythropoiesis pathway regulates extramedullary stress erythropoiesis, which occurs primarily in the murine spleen or in the case of splenectomized mice, in the adult liver. ..
  2. Parikh P, Hao Y, Hosseinkhani M, Patil S, Huntley G, Tessier Lavigne M, et al. Regeneration of axons in injured spinal cord by activation of bone morphogenetic protein/Smad1 signaling pathway in adult neurons. Proc Natl Acad Sci U S A. 2011;108:E99-107 pubmed publisher
    ..Smad1 signaling can be effectively manipulated by an adeno-associated virus (AAV) vector encoding BMP4 delivered by a clinically applicable and minimally invasive technique, an approach devoid of unwanted abnormalities ..
  3. Mysorekar I, Isaacson Schmid M, Walker J, Mills J, Hultgren S. Bone morphogenetic protein 4 signaling regulates epithelial renewal in the urinary tract in response to uropathogenic infection. Cell Host Microbe. 2009;5:463-75 pubmed publisher
    ..Together, our study indicates that UPEC infection but not chemical injury activates the USC niche, and Bmp signaling is required for regulation of the USC response to infection. ..
  4. Norden J, Grieskamp T, Lausch E, van Wijk B, van den Hoff M, Englert C, et al. Wt1 and retinoic acid signaling in the subcoelomic mesenchyme control the development of the pleuropericardial membranes and the sinus horns. Circ Res. 2010;106:1212-20 pubmed publisher
    ..Thus, our results provide novel insight into the genetic and cellular pathways regulating the posterior extension of the mammalian heart and the formation of its coelomic lining. ..
  5. Fotaki V, Smith R, Pratt T, Price D. Foxg1 is required to limit the formation of ciliary margin tissue and Wnt/?-catenin signalling in the developing nasal retina of the mouse. Dev Biol. 2013;380:299-313 pubmed publisher
    ..Our results reveal a new role of Foxg1 in limiting CM development in the nasal peripheral retina and add a new molecular player in the developmental network involved in CM specification. ..
  6. Villacorte M, Suzuki K, Hayashi K, de Sousa Lopes S, Haraguchi R, Taketo M, et al. Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation. Biochem Biophys Res Commun. 2010;391:1653-7 pubmed publisher
    ..Elucidation of the potential mechanisms underlying such D/ID development is an urgent medical issue to be solved. This work would be one of the first studies showing essential growth factor cascades in the D/ID formation. ..
  7. Miyagawa S, Moon A, Haraguchi R, Inoue C, Harada M, Nakahara C, et al. Dosage-dependent hedgehog signals integrated with Wnt/beta-catenin signaling regulate external genitalia formation as an appendicular program. Development. 2009;136:3969-78 pubmed publisher
    ..Our results provide new insights into the integration of growth factor signaling in the appendicular developmental programs that regulate external genitalia development...
  8. Sala F, del Moral P, Tiozzo C, Alam D, Warburton D, Grikscheit T, et al. FGF10 controls the patterning of the tracheal cartilage rings via Shh. Development. 2011;138:273-82 pubmed publisher
    ..We propose that disturbed balances of Fgf10 and Shh may explain a subset of human tracheomalacia without tracheo-esophageal fistula or tracheal atresia...
  9. Wang J, Greene S, Bonilla Claudio M, Tao Y, Zhang J, Bai Y, et al. Bmp signaling regulates myocardial differentiation from cardiac progenitors through a MicroRNA-mediated mechanism. Dev Cell. 2010;19:903-12 pubmed publisher
    ..Bmp2 and Bmp4 regulate OFT myocardial differentiation via regulation of the miRNA-17-92 cluster...
  10. Reid B, Yang H, Melvin V, Taketo M, Williams T. Ectodermal Wnt/?-catenin signaling shapes the mouse face. Dev Biol. 2011;349:261-9 pubmed publisher
  11. Bénazet J, Bischofberger M, Tiecke E, Gonçalves A, Martin J, Zuniga A, et al. A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning. Science. 2009;323:1050-3 pubmed publisher
    ..By combining mouse molecular genetics with mathematical modeling, we showed that BMP4 first initiates and SHH then propagates e-m feedback signaling through differential transcriptional regulation of ..
  12. Chen J, Lan Y, Baek J, Gao Y, Jiang R. Wnt/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development. Dev Biol. 2009;334:174-85 pubmed publisher
    ..Together, these results indicate that activation of the mesenchymal odontogenic program during early tooth development requires concerted actions of Bmp, Fgf and Wnt signaling from the presumptive dental epithelium to the mesenchyme...
  13. Bai Y, Wang J, Morikawa Y, Bonilla Claudio M, Klysik E, Martin J. Bmp signaling represses Vegfa to promote outflow tract cushion development. Development. 2013;140:3395-402 pubmed publisher
    ..We investigated Bmp signaling in mouse OFT development by conditionally deleting both Bmp4 and Bmp7 in the second heart field (SHF)...
  14. He F, Xiong W, Wang Y, Matsui M, Yu X, Chai Y, et al. Modulation of BMP signaling by Noggin is required for the maintenance of palatal epithelial integrity during palatogenesis. Dev Biol. 2010;347:109-21 pubmed publisher
    ..Among the extracellular BMP antagonists is Noggin, which preferentialy binds to BMP2, BMP4 and BMP7, all of which are expressed in the developing palatal shelves...
  15. Pan W, Jin Y, STANGER B, Kiernan A. Notch signaling is required for the generation of hair cells and supporting cells in the mammalian inner ear. Proc Natl Acad Sci U S A. 2010;107:15798-803 pubmed publisher
    ..These data indicate that Notch specifies sensory progenitors in the inner ear, and that induction of Notch may be important for regenerating or replacing hair cells and supporting cells in the mammalian inner ear. ..
  16. Tan T, Huang Y, Chang J, Lin J, Fong Y, Kuo C, et al. CCN3 increases BMP-4 expression and bone mineralization in osteoblasts. J Cell Physiol. 2012;227:2531-41 pubmed publisher
    ..Taken together, our results provide evidence that CCN3 enhances BMP-4 expression and bone nodule formation in osteoblasts, and that the integrin receptor, ILK, p38, JNK, and AP-1 signaling pathways may be involved. ..
  17. Basch M, Ohyama T, Segil N, Groves A. Canonical Notch signaling is not necessary for prosensory induction in the mouse cochlea: insights from a conditional mutant of RBPjkappa. J Neurosci. 2011;31:8046-58 pubmed publisher
    ..Our results indicate that canonical Notch signaling is not necessary for prosensory specification in the mouse cochlea, suggesting that other signaling pathways may specify this highly derived sensory organ. ..
  18. Du Y, Xiao Q, Yip H. Regulation of retinal progenitor cell differentiation by bone morphogenetic protein 4 is mediated by the smad/id cascade. Invest Ophthalmol Vis Sci. 2010;51:3764-73 pubmed publisher
    ..Retinal progenitor cells (RPCs) were used to study the effects of BMP4 on retinal cell differentiation and regulation of Id protein expression. RESULTS...
  19. Seifert A, Yamaguchi T, Cohn M. Functional and phylogenetic analysis shows that Fgf8 is a marker of genital induction in mammals but is not required for external genital development. Development. 2009;136:2643-51 pubmed publisher
    ..We propose that induction of external genitalia involves an epithelial-epithelial interaction at the cloacal membrane, and suggest that the cloacal ectoderm may be the source of the genital initiation signal...
  20. Uchimura T, Komatsu Y, Tanaka M, McCann K, Mishina Y. Bmp2 and Bmp4 genetically interact to support multiple aspects of mouse development including functional heart development. Genesis. 2009;47:374-84 pubmed publisher
    ..Current data indicate that the dosage of BMPs is tightly regulated for normal development in mice. Since Bmp2 or Bmp4 homozygous mutant mice show early embryonic lethality, we generated compound heterozygous mice for Bmp2 and Bmp4 to ..
  21. He F, Hu X, Xiong W, Li L, Lin L, Shen B, et al. Directed Bmp4 expression in neural crest cells generates a genetic model for the rare human bony syngnathia birth defect. Dev Biol. 2014;391:170-81 pubmed publisher
    ..Here we present evidence that transgenic expression of Bmp4 in neural crest cells causes a series of craniofacial malformations in mice, including a bony fusion between the ..
  22. Wang C, Gargollo P, Guo C, Tang T, Mingin G, Sun Y, et al. Six1 and Eya1 are critical regulators of peri-cloacal mesenchymal progenitors during genitourinary tract development. Dev Biol. 2011;360:186-94 pubmed publisher
    ..Thus, Six1 and Eya1 are key regulators of both upper and lower urinary tract morphogenesis. Results from this study uncover essential roles of the PCM progenitors during genitourinary tract formation...
  23. Bonilla Claudio M, Wang J, Bai Y, Klysik E, Selever J, Martin J. Bmp signaling regulates a dose-dependent transcriptional program to control facial skeletal development. Development. 2012;139:709-19 pubmed publisher
    We performed an in depth analysis of Bmp4, a critical regulator of development, disease, and evolution, in cranial neural crest (CNC)...
  24. Funato N, Nakamura M, Richardson J, Srivastava D, Yanagisawa H. Tbx1 regulates oral epithelial adhesion and palatal development. Hum Mol Genet. 2012;21:2524-37 pubmed publisher
    ..Our present study reveals new pathogenesis of incomplete and submucous cleft palate during mammalian palatogenesis. ..
  25. Jumlongras D, Lachke S, O Connell D, Aboukhalil A, Li X, Choe S, et al. An evolutionarily conserved enhancer regulates Bmp4 expression in developing incisor and limb bud. PLoS ONE. 2012;7:e38568 pubmed publisher
    To elucidate the transcriptional regulation of Bmp4 expression during organogenesis, we used phylogenetic footprinting and transgenic reporter analyses to identify Bmp4 cis-regulatory modules (CRMs)...
  26. Self M, Geng X, Oliver G. Six2 activity is required for the formation of the mammalian pyloric sphincter. Dev Biol. 2009;334:409-17 pubmed publisher
    ..Our data reveal that several genes known to be important for pyloric sphincter formation in the chick (e.g., Bmp4, Bmpr1b, Nkx2.5, Sox9, and Gremlin) also appear to be required for the formation of this structure in mammals...
  27. Vervoort R, Ceulemans H, Van Aerschot L, D Hooge R, David G. Genetic modification of the inner ear lateral semicircular canal phenotype of the Bmp4 haplo-insufficient mouse. Biochem Biophys Res Commun. 2010;394:780-5 pubmed publisher
    In the mouse, development of the lateral semicircular canal of the inner ear is sensitive to Bmp4 heterozygosity...
  28. Danesh S, Villasenor A, Chong D, Soukup C, Cleaver O. BMP and BMP receptor expression during murine organogenesis. Gene Expr Patterns. 2009;9:255-65 pubmed publisher
    ..Here, we present a detailed study of the developmental expression profiles of three BMP ligands (Bmp2, Bmp4, Bmp7) and three BMP receptors (Bmpr1a, Bmpr1b, and BmprII), as well as their molecular antagonist (noggin), in the ..
  29. Koo S, Hill J, Hwang C, Lin Z, Millen K, Wu D. Lmx1a maintains proper neurogenic, sensory, and non-sensory domains in the mammalian inner ear. Dev Biol. 2009;333:14-25 pubmed publisher
    ..Furthermore, aberrant and ectopic sensory organs are observed; most striking among these is vestibular-like hair cells located in the cochlear duct. ..
  30. Matsushima D, Heavner W, Pevny L. Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6. Development. 2011;138:443-54 pubmed publisher
    ..Collectively, these results demonstrate that precise regulation of the ratio of SOX2 to PAX6 is necessary to ensure accurate progenitor cell specification, and place SOX2 as a decisive factor of neural competence in the retina. ..
  31. Talamillo A, Delgado I, Nakamura T, de Vega S, Yoshitomi Y, Unda F, et al. Role of Epiprofin, a zinc-finger transcription factor, in limb development. Dev Biol. 2010;337:363-74 pubmed publisher
  32. Bensoussan Trigano V, Lallemand Y, Saint Cloment C, Robert B. Msx1 and Msx2 in limb mesenchyme modulate digit number and identity. Dev Dyn. 2011;240:1190-202 pubmed publisher
    ..With this strategy, we demonstrate that mesenchymal expression of Msx1 and Msx2 is required for proper Shh and Bmp4 signaling to specify digit number and identity.
  33. Compagnucci C, Debiais Thibaud M, Coolen M, Fish J, Griffin J, Bertocchini F, et al. Pattern and polarity in the development and evolution of the gnathostome jaw: both conservation and heterotopy in the branchial arches of the shark, Scyliorhinus canicula. Dev Biol. 2013;377:428-48 pubmed publisher
  34. Gordon J, Patel S, Mishina Y, Manley N. Evidence for an early role for BMP4 signaling in thymus and parathyroid morphogenesis. Dev Biol. 2010;339:141-54 pubmed publisher
    ..Previous gene expression and functional analyses have suggested a role for BMP4 signaling in early thymus organogenesis...
  35. Pan N, Jahan I, Kersigo J, Kopecky B, Santi P, Johnson S, et al. Conditional deletion of Atoh1 using Pax2-Cre results in viable mice without differentiated cochlear hair cells that have lost most of the organ of Corti. Hear Res. 2011;275:66-80 pubmed publisher
    ..the organ of Corti is reduced to two rows of cells wedged between flanking markers of the organ of Corti (Fgf10 and Bmp4). These two rows of cells (instead of five rows of supporting cells) are positive for Prox1 in neonates...
  36. Park J, Zhang J, Moro A, Kushida M, Wegner M, Kim P. Regulation of Sox9 by Sonic Hedgehog (Shh) is essential for patterning and formation of tracheal cartilage. Dev Dyn. 2010;239:514-26 pubmed publisher
    ..Both exogenous Bmp4 and Noggin rescue cartilage phenotype in Shh(-/-) tracheal culture, while promoting excessive cartilage development ..
  37. Lenton K, James A, Manu A, Brugmann S, Birker D, Nelson E, et al. Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling. Genesis. 2011;49:784-96 pubmed publisher
    ..In conjunction with the newly recognized roles of Hedgehog deregulation in craniosynostosis, our study defines Ihh as an important positive regulator of cranial bone ossification. ..
  38. Ohyama T, Basch M, Mishina Y, Lyons K, Segil N, Groves A. BMP signaling is necessary for patterning the sensory and nonsensory regions of the developing mammalian cochlea. J Neurosci. 2010;30:15044-51 pubmed publisher
    ..b>BMP4 upregulates markers of the future outer sulcus and downregulates marker genes of Kölliker's organ in cochlear ..
  39. Walker K, Sims Lucas S, Caruana G, Cullen McEwen L, Li J, Sarraj M, et al. Betaglycan is required for the establishment of nephron endowment in the mouse. PLoS ONE. 2011;6:e18723 pubmed publisher
    ..5-e14.5 kidneys demonstrated that heterozygous kidneys exhibited a transient decrease in Bmp4 expression at e11...
  40. Yamamoto N, Chang W, Kelley M. Rbpj regulates development of prosensory cells in the mammalian inner ear. Dev Biol. 2011;353:367-79 pubmed publisher
    ..These results suggest important roles for Rbpj and notch signaling in multiple aspects of inner ear development including prosensory cell maturation, cellular differentiation and survival. ..
  41. Saitoh M, Shirakihara T, Fukasawa A, Horiguchi K, Sakamoto K, Sugiya H, et al. Basolateral BMP signaling in polarized epithelial cells. PLoS ONE. 2013;8:e62659 pubmed publisher
    ..We conclude that BMPs maintain epithelial polarity via intracellular signaling from basolaterally localized BMP receptors. ..
  42. Li L, Lin M, Wang Y, Cserjesi P, Chen Z, Chen Y. BmprIa is required in mesenchymal tissue and has limited redundant function with BmprIb in tooth and palate development. Dev Biol. 2011;349:451-61 pubmed publisher
    ..Our results demonstrate an essential role for BmprIa in the mesenchymal component and a limited functional redundancy between BmprIa and BmprIb in a tissue-specific manner during tooth and palate development...
  43. Ueki Y, Reh T. Activation of BMP-Smad1/5/8 signaling promotes survival of retinal ganglion cells after damage in vivo. PLoS ONE. 2012;7:e38690 pubmed publisher
    ..Moreover, treatment of the retina with exogenous BMP4 along with NMDA damage led to a significant rescue of retinal ganglion cells...
  44. Chen D, Jarrell A, Guo C, Lang R, Atit R. Dermal ?-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation. Development. 2012;139:1522-33 pubmed publisher
    ..These data reveal functional roles for dermal Wnt signaling/?-catenin in fibroblast proliferation and in the epidermal hair follicle initiation program. ..
  45. Harandi O, Hedge S, Wu D, McKeone D, Paulson R. Murine erythroid short-term radioprotection requires a BMP4-dependent, self-renewing population of stress erythroid progenitors. J Clin Invest. 2010;120:4507-19 pubmed publisher
    ..In this study we found that the bone morphogenetic protein 4-dependent (BMP4-dependent) stress erythropoiesis pathway was required and specific for erythroid short-..
  46. Törnqvist G, Sandberg A, Hägglund A, Carlsson L. Cyclic expression of lhx2 regulates hair formation. PLoS Genet. 2010;6:e1000904 pubmed publisher
  47. Jang C, Gao L, Dickinson M, Behringer R. Bmp4-directed nuclear cyan fluorescent protein provides a tool for live imaging and reveals cellular resolution of Bmp4 expression patterns during embryogenesis. Int J Dev Biol. 2010;54:931-8 pubmed publisher
    ..Bmp4 (Bone Morphogenetic Protein 4) is expressed in the mesenchymal tissue surrounding developing hair follicles...
  48. Liu B, Feng D, Lin G, Cao M, Kan Y, Cunha G, et al. Signalling molecules involved in mouse bladder smooth muscle cellular differentiation. Int J Dev Biol. 2010;54:175-80 pubmed publisher
    ..Genes downstream of Shh are differentially expressed in the prospective submucosa vs. the peripheral bladder mesenchyme as a function gestation age and smooth muscle differentiation...
  49. Tsuji K, Cox K, Gamer L, Graf D, Economides A, Rosen V. Conditional deletion of BMP7 from the limb skeleton does not affect bone formation or fracture repair. J Orthop Res. 2010;28:384-9 pubmed publisher
    ..Our data suggest that other BMPs present in adult bone are sufficient to compensate for the absence of BMP7. ..
  50. Lallemand Y, Bensoussan V, Cloment C, Robert B. Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb. Dev Biol. 2009;331:189-98 pubmed publisher
  51. Choi K, Lee C, Maatouk D, Harfe B. Bmp2, Bmp4 and Bmp7 are co-required in the mouse AER for normal digit patterning but not limb outgrowth. PLoS ONE. 2012;7:e37826 pubmed publisher
    ..In this report, we genetically removed the three known AER-expressed Bmp ligands, Bmp2, Bmp4 and Bmp7 from the AER of the limb bud using floxed conditional alleles and the Msx2-cre allele...
  52. Lin C, Yin Y, Bell S, Veith G, Chen H, Huh S, et al. Delineating a conserved genetic cassette promoting outgrowth of body appendages. PLoS Genet. 2013;9:e1003231 pubmed publisher
    ..These observations indicate that a conserved WNT-SP8-FGF8 genetic cassette is employed by both appendages for promoting outgrowth, and suggest a deep homology shared by the limb and external genitalia. ..
  53. Lan Y, Ovitt C, Cho E, Maltby K, Wang Q, Jiang R. Odd-skipped related 2 (Osr2) encodes a key intrinsic regulator of secondary palate growth and morphogenesis. Development. 2004;131:3207-16 pubmed
    ..These data identify Osr2 as a key intrinsic regulator of palatal growth and patterning. ..
  54. Dudley A, Robertson E. Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos. Dev Dyn. 1997;208:349-62 pubmed
    ..The variable expressivity of the eye defect correlates with partially overlapping BMP4 and BMP7 expression domains during early eye induction...