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Gene Ontology Classifications
bone morphogenetic protein 4

Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Bmp4. (This text reflects annotations as of Tuesday, May 26, 2015.)
Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. The superfamily includes large families of growth and differentiation factors. Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. This particular family member plays an important role in the onset of endochondral bone formation in humans, and a reduction in expression has been associated with a variety of bone diseases, including the heritable disorder Fibrodysplasia Ossificans Progressiva. Alternative splicing in the 5' untranslated region of this gene has been described and three variants are described, all encoding an identical protein. [provided by RefSeq, Jul 2008]
Summary text based on GO annotations supported by experimental evidence in mouse
Summary text based on GO annotations supported by experimental evidence in other organisms
Summary text based on GO annotations supported by structural data
Summary text for additional MGI annotations
  1. Almahbobi G et al. (2005) Computer-based detection of neonatal changes to branching morphogenesis reveals different mechanisms of and predicts prostate enlargement in mice haplo-insufficient for bone morphogenetic protein 4. J Pathol, 206:52-61. (PubMed:15772937)
  2. Astorga J et al. (2007) Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4. Development, 134:3753-61. (PubMed:17881493)
  3. Babitt JL et al. (2005) Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor. J Biol Chem, 280:29820-7. (PubMed:15975920)
  4. Babitt JL et al. (2006) Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet, 38:531-9. (PubMed:16604073)
  5. Begue-Kirn C et al. (1994) Comparative analysis of TGF beta s, BMPs, IGF1, msxs, fibronectin, osteonectin and bone sialoprotein gene expression during normal and in vitro-induced odontoblast differentiation. Int J Dev Biol, 38:405-20. (PubMed:7848824)
  6. Biben C et al. (1998) Murine cerberus homologue mCer-1: a candidate anterior patterning molecule. Dev Biol, 194:135-51. (PubMed:9501024)
  7. Blitz E et al. (2009) Bone ridge patterning during musculoskeletal assembly is mediated through SCX regulation of Bmp4 at the tendon-skeleton junction. Dev Cell, 17:861-73. (PubMed:20059955)
  8. Brenner-Anantharam A et al. (2007) Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4 signaling. Development, 134:1967-75. (PubMed:17442697)
  9. Busygina TV et al. (2001) [Effect of genotype and social stress on cAMP- and substrate-dependent mechanisms of regulating hormonal function of testis in mice] Genetika, 37:649-56. (PubMed:11436557)
  10. Caubit X et al. (2008) Teashirt 3 is necessary for ureteral smooth muscle differentiation downstream of SHH and BMP4. Development, 135:3301-10. (PubMed:18776146)
  11. Chen Y et al. (1996) Msx1 controls inductive signaling in mammalian tooth morphogenesis. Development, 122:3035-44. (PubMed:8898217)
  12. Cheng X et al. (2006) Central roles of the roof plate in telencephalic development and holoprosencephaly. J Neurosci, 26:7640-9. (PubMed:16855091)
  13. Cho KW et al. (2006) Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gland development. Proc Natl Acad Sci U S A, 103:16788-93. (PubMed:17071745)
  14. Cook C et al. (2007) Noggin is required for normal lobe patterning and ductal budding in the mouse prostate. Dev Biol, 312:217-30. (PubMed:18028901)
  15. de Sousa Lopes SM et al. (2004) BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. Genes Dev, 18:1838-49. (PubMed:15289457)
  16. Dunn NR et al. (1997) Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol, 188:235-47. (PubMed:9268572)
  17. Eblaghie MC et al. (2006) Evidence that autocrine signaling through Bmpr1a regulates the proliferation, survival and morphogenetic behavior of distal lung epithelial cells. Dev Biol, 291:67-82. (PubMed:16414041)
  18. Furuta Y et al. (1998) BMP4 is essential for lens induction in the mouse embryo. Genes Dev, 12:3764-75. (PubMed:9851982)
  19. Hager-Theodorides AL et al. (2002) Bone morphogenetic protein 2/4 signaling regulates early thymocyte differentiation. J Immunol, 169:5496-504. (PubMed:12421925)
  20. Hodge LK et al. (2007) Retrograde BMP signaling regulates trigeminal sensory neuron identities and the formation of precise face maps. Neuron, 55:572-86. (PubMed:17698011)
  21. Hollnagel A et al. (1999) Id genes are direct targets of bone morphogenetic protein induction in embryonic stem cells. J Biol Chem, 274:19838-45. (PubMed:10391928)
  22. Hu Q et al. (2004) Restriction of BMP4 activity domains in the developing neural tube of the mouse embryo. EMBO Rep, 5:734-9. (PubMed:15218525)
  23. Itaranta P et al. (2006) Wnt-4 signaling is involved in the control of smooth muscle cell fate via Bmp-4 in the medullary stroma of the developing kidney. Dev Biol, 293:473-83. (PubMed:16546160)
  24. Jasuja R et al. (2004) Cell-surface heparan sulfate proteoglycans potentiate chordin antagonism of bone morphogenetic protein signaling and are necessary for cellular uptake of chordin. J Biol Chem, 279:51289-97. (PubMed:15381701)
  25. Jiao K et al. (2003) An essential role of Bmp4 in the atrioventricular septation of the mouse heart. Genes Dev, 17:2362-7. (PubMed:12975322)
  26. Johansson BM et al. (1995) Evidence for involvement of activin A and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development. Mol Cell Biol, 15:141-51. (PubMed:7799920)
  27. Karamboulas K et al. (2010) Regulation of BMP-dependent chondrogenesis in early limb mesenchyme by TGFbeta signals. J Cell Sci, 123:2068-76. (PubMed:20501701)
  28. Kassai Y et al. (2005) Regulation of mammalian tooth cusp patterning by ectodin. Science, 309:2067-70. (PubMed:16179481)
  29. Katagiri T et al. (1998) Skeletal abnormalities in doubly heterozygous Bmp4 and Bmp7 mice. Dev Genet, 22:340-8. (PubMed:9664686)
  30. Kim HJ et al. (1998) FGF-, BMP- and Shh-mediated signalling pathways in the regulation of cranial suture morphogenesis and calvarial bone development. Development, 125:1241-51. (PubMed:9477322)
  31. Lamm ML et al. (2001) Mesenchymal factor bone morphogenetic protein 4 restricts ductal budding and branching morphogenesis in the developing prostate. Dev Biol, 232:301-14. (PubMed:11401393)
  32. Laurikkala J et al. (2003) Identification of a secreted BMP antagonist, ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot. Dev Biol, 264:91-105. (PubMed:14623234)
  33. Lee D et al. (2008) ER71 acts downstream of BMP, Notch, and Wnt signaling in blood and vessel progenitor specification. Cell Stem Cell, 2:497-507. (PubMed:18462699)
  34. Lenox LE et al. (2005) BMP4 and Madh5 regulate the erythroid response to acute anemia. Blood, 105:2741-8. (PubMed:15591122)
  35. Levinson RS et al. (2005) Foxd1-dependent signals control cellularity in the renal capsule, a structure required for normal renal development. Development, 132:529-39. (PubMed:15634693)
  36. Li W et al. (1998) Neuronal differentiation of precursors in the neocortical ventricular zone is triggered by BMP. J Neurosci, 18:8853-62. (PubMed:9786991)
  37. Li Y et al. (2008) Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis. Dev Biol, 322:145-55. (PubMed:18692041)
  38. Liu W et al. (2005) Threshold-specific requirements for Bmp4 in mandibular development. Dev Biol, 283:282-93. (PubMed:15936012)
  39. Liu W et al. (2005) Distinct functions for Bmp signaling in lip and palate fusion in mice. Development, 132:1453-61. (PubMed:15716346)
  40. Liu W et al. (2004) Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling. Proc Natl Acad Sci U S A, 101:4489-94. (PubMed:15070745)
  41. Mahlapuu M et al. (2001) Haploinsufficiency of the forkhead gene Foxf1, a target for sonic hedgehog signaling, causes lung and foregut malformations. Development, 128:2397-406. (PubMed:11493558)
  42. Mailleux AA et al. (2005) Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage. Development, 132:2157-66. (PubMed:15800000)
  43. McMahon JA et al. (1998) Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev, 12:1438-52. (PubMed:9585504)
  44. Michos O et al. (2007) Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis. Development, 134:2397-405. (PubMed:17522159)
  45. Misra K et al. (2010) A critical role for sFRP proteins in maintaining caudal neural tube closure in mice via inhibition of BMP signaling. Dev Biol, 337:74-83. (PubMed:19850029)
  46. Miyazaki Y et al. (2003) Evidence that bone morphogenetic protein 4 has multiple biological functions during kidney and urinary tract development. Kidney Int, 63:835-44. (PubMed:12631064)
  47. Monuki ES et al. (2001) Patterning of the dorsal telencephalon and cerebral cortex by a roof plate-lhx2 pathway. Neuron, 32:591-604. (PubMed:11719201)
  48. Moser M et al. (2003) BMPER, a novel endothelial cell precursor-derived protein, antagonizes bone morphogenetic protein signaling and endothelial cell differentiation. Mol Cell Biol, 23:5664-79. (PubMed:12897139)
  49. Murashima-Suginami A et al. (2007) Rudiment incisors survive and erupt as supernumerary teeth as a result of USAG-1 abrogation. Biochem Biophys Res Commun, 359:549-55. (PubMed:17555714)
  50. Nakayama N et al. (2004) A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in chondrocytes of developing cartilage and osteoarthritic joint cartilage. Development, 131:229-40. (PubMed:14660436)
  51. Neubuser A et al. (1997) Antagonistic interactions between FGF and BMP signaling pathways: a mechanism for positioning the sites of tooth formation. Cell, 90:247-55. (PubMed:9244299)
  52. Nie X et al. (2011) Six1 regulates Grem1 expression in the metanephric mesenchyme to initiate branching morphogenesis. Dev Biol, 352:141-51. (PubMed:21281623)
  53. Oka C et al. (2004) HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins. Development, 131:1041-53. (PubMed:14973287)
  54. Oxburgh L et al. (2005) BMP4 substitutes for loss of BMP7 during kidney development. Dev Biol, 286:637-46. (PubMed:16154126)
  55. Paine-Saunders S et al. (2000) glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development. Dev Biol, 225:179-87. (PubMed:10964473)
  56. Phelan JP. (1992) Genetic variability and rodent models of human aging. Exp Gerontol, 27:147-59. (PubMed:1521591)
  57. Que J et al. (2006) Morphogenesis of the trachea and esophagus: current players and new roles for noggin and Bmps. Differentiation, 74:422-37. (PubMed:16916379)
  58. Rajagopal J et al. (2008) Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme. Development, 135:1625-34. (PubMed:18367557)
  59. Sirard C et al. (1998) The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev, 12:107-19. (PubMed:9420335)
  60. Stottmann RW et al. (2006) The BMP antagonist Noggin promotes cranial and spinal neurulation by distinct mechanisms. Dev Biol, 295:647-63. (PubMed:16712836)
  61. Suzuki Y et al. (2010) BMP-9 induces proliferation of multiple types of endothelial cells in vitro and in vivo. J Cell Sci, 123:1684-92. (PubMed:20406889)
  62. Takaoka K et al. (1993) Gene cloning and expression of a bone morphogenetic protein derived from a murine osteosarcoma. Clin Orthop, 294:344-52. (PubMed:8358941)
  63. Takuma N et al. (1998) Formation of Rathke's pouch requires dual induction from the diencephalon. Development, 125:4835-40. (PubMed:9806931)
  64. Thesleff I et al. (1996) Molecular mechanisms of cell and tissue interactions during early tooth development. Anat Rec, 245:151-61. (PubMed:8769660)
  65. Tocharus J et al. (2004) Developmentally regulated expression of mouse HtrA3 and its role as an inhibitor of TGF-beta signaling. Dev Growth Differ, 46:257-74. (PubMed:15206957)
  66. Truksa J et al. (2009) Two BMP responsive elements, STAT, and bZIP/HNF4/COUP motifs of the hepcidin promoter are critical for BMP, SMAD1, and HJV responsiveness. Blood, 113:688-95. (PubMed:18997172)
  67. Ueda H et al. (2008) Bmp in podocytes is essential for normal glomerular capillary formation. J Am Soc Nephrol, 19:685-94. (PubMed:18272846)
  68. Vainio S et al. (1993) Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell, 75:45-58. (PubMed:8104708)
  69. Vezina CM et al. (2008) Retinoic acid induces prostatic bud formation. Dev Dyn, 237:1321-33. (PubMed:18393306)
  70. Wang XP et al. (2004) Follistatin regulates enamel patterning in mouse incisors by asymmetrically inhibiting BMP signaling and ameloblast differentiation. Dev Cell, 7:719-30. (PubMed:15525533)
  71. Winnier G et al. (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev, 9:2105-16. (PubMed:7657163)
  72. Xia Y et al. (2007) Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4. J Biol Chem, 282:18129-40. (PubMed:17472960)
  73. Yamaji M et al. (2008) Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet, 40:1016-22. (PubMed:18622394)
  74. Yu L et al. (2007) Shox2 is required for chondrocyte proliferation and maturation in proximal limb skeleton. Dev Biol, 306:549-59. (PubMed:17481601)
  75. Zakin L et al. (2004) Inactivation of mouse Twisted gastrulation reveals its role in promoting Bmp4 activity during forebrain development. Development, 131:413-24. (PubMed:14681194)
  76. Zhang Y et al. (1999) Msx1 is required for the induction of Patched by Sonic hedgehog in the mammalian tooth germ. Dev Dyn, 215:45-53. (PubMed:10340755)
  77. Zhang Y et al. (2000) A new function of BMP4: dual role for BMP4 in regulation of Sonic hedgehog expression in the mouse tooth germ. Development, 127:1431-43. (PubMed:10704389)
  78. Zhang Z et al. (2003) Msx1/Bmp4 genetic pathway regulates mammalian alveolar bone formation via induction of Dlx5 and Cbfa1. Mech Dev, 120:1469-79. (PubMed:14654219)
  79. Zhu NL et al. (2007) TNF-alpha represses transcription of human Bone Morphogenetic Protein-4 in lung epithelial cells. Gene, 393:70-80. (PubMed:17350185)

Go Annotations in Tabular Form (Text View) (GO Graph)

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Gene Ontology Evidence Code Abbreviations:

  EXP Inferred from experiment
  IAS Inferred from ancestral sequence
  IBA Inferred from biological aspect of ancestor
  IBD Inferred from biological aspect of descendant
  IC Inferred by curator
  IDA Inferred from direct assay
  IEA Inferred from electronic annotation
  IGI Inferred from genetic interaction
  IKR Inferred from key residues
  IMP Inferred from mutant phenotype
  IMR Inferred from missing residues
  IPI Inferred from physical interaction
  IRD Inferred from rapid divergence
  ISS Inferred from sequence or structural similarity
  ISO Inferred from sequence orthology
  ISA Inferred from sequence alignment
  ISM Inferred from sequence model
  NAS Non-traceable author statement
  ND No biological data available
  RCA Reviewed computational analysis
  TAS Traceable author statement


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