Bone morphogenetic protein 4

Bone morphogenetic protein 4

Bone morphogenetic protein 4, also known as BMP4, is a human gene.

section_title =
summary_text = 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. [cite web | title = Entrez Gene: BMP4 bone morphogenetic protein 4| url =| accessdate = ]

BMP4 is a polypeptide belonging to the TGF-β superfamily of proteins. It, like other bone morphogenetic proteins, is involved in bone and cartilage development, specifically tooth and limb development and fracture repair. It has been shown to be involved in muscle development, bone mineralization, and uteric bud development. BMP4 has also been implicated in Fibrodysplasia Ossificans Progressiva in which it is underexpressed.

In human embryonic development, BMP4 is a critical signaling molecule required for the early differentiation of the embryo and establishing of a dorsal-ventral axis. BMP4 is secreted from the dorsal portion of the notochord, and it acts in concert with sonic hedgehog (released from the ventral portion of the notochord) to establish a dorsal-ventral axis for the differentiation of later structures.

BMP4 stimulates differentiation of overlying ectodermal tissue. Inhibition of the BMP4 signal (by chordin, noggin, or follistatin) causes the ectoderm to differentiate into the neural plate. If these cells also receive signals from FGF, they will differentiate into the spinal cord; in the absence of FGF the cells become brain tissue.


Further reading

citations =
*cite journal | author=Wozney JM, Rosen V, Celeste AJ, "et al." |title=Novel regulators of bone formation: molecular clones and activities. |journal=Science |volume=242 |issue= 4885 |pages= 1528–34 |year= 1989 |pmid= 3201241 |doi=
*cite journal | author=van den Wijngaard A, Weghuis DO, Boersma CJ, "et al." |title=Fine mapping of the human bone morphogenetic protein-4 gene (BMP4) to chromosome 14q22-q23 by in situ hybridization. |journal=Genomics |volume=27 |issue= 3 |pages= 559–60 |year= 1995 |pmid= 7558046 |doi=
*cite journal | author=Oida S, Iimura T, Maruoka Y, "et al." |title=Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human placental cDNA library. |journal=DNA Seq. |volume=5 |issue= 5 |pages= 273–5 |year= 1995 |pmid= 7579580 |doi=
*cite journal | author=Rosenzweig BL, Imamura T, Okadome T, "et al." |title=Cloning and characterization of a human type II receptor for bone morphogenetic proteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue= 17 |pages= 7632–6 |year= 1995 |pmid= 7644468 |doi=
*cite journal | author=Nohno T, Ishikawa T, Saito T, "et al." |title=Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors. |journal=J. Biol. Chem. |volume=270 |issue= 38 |pages= 22522–6 |year= 1995 |pmid= 7673243 |doi=
*cite journal | author=Yamaji N, Celeste AJ, Thies RS, "et al." |title=A mammalian serine/threonine kinase receptor specifically binds BMP-2 and BMP-4. |journal=Biochem. Biophys. Res. Commun. |volume=205 |issue= 3 |pages= 1944–51 |year= 1995 |pmid= 7811286 |doi= 10.1006/bbrc.1994.2898
*cite journal | author=Harris SE, Harris MA, Mahy P, "et al." |title=Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells. |journal=Prostate |volume=24 |issue= 4 |pages= 204–11 |year= 1994 |pmid= 8146069 |doi=
*cite journal | author=van den Wijngaard A, van Kraay M, van Zoelen EJ, "et al." |title=Genomic organization of the human bone morphogenetic protein-4 gene: molecular basis for multiple transcripts. |journal=Biochem. Biophys. Res. Commun. |volume=219 |issue= 3 |pages= 789–94 |year= 1996 |pmid= 8645259 |doi= 10.1006/bbrc.1996.0312
*cite journal | author=Nishitoh H, Ichijo H, Kimura M, "et al." |title=Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5. |journal=J. Biol. Chem. |volume=271 |issue= 35 |pages= 21345–52 |year= 1996 |pmid= 8702914 |doi=
*cite journal | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791–806 |year= 1997 |pmid= 8889548 |doi=
*cite journal | author=Shore EM, Xu M, Shah PB, "et al." |title=The human bone morphogenetic protein 4 (BMP-4) gene: molecular structure and transcriptional regulation. |journal=Calcif. Tissue Int. |volume=63 |issue= 3 |pages= 221–9 |year= 1998 |pmid= 9701626 |doi=
*cite journal | author=Tucker AS, Matthews KL, Sharpe PT |title=Transformation of tooth type induced by inhibition of BMP signaling. |journal=Science |volume=282 |issue= 5391 |pages= 1136–8 |year= 1998 |pmid= 9804553 |doi=
*cite journal | author=Van den Wijngaard A, Pijpers MA, Joosten PH, "et al." |title=Functional characterization of two promoters in the human bone morphogenetic protein-4 gene. |journal=J. Bone Miner. Res. |volume=14 |issue= 8 |pages= 1432–41 |year= 1999 |pmid= 10457277 |doi=
*cite journal | author=Li W, LoTurco JJ |title=Noggin is a negative regulator of neuronal differentiation in developing neocortex. |journal=Dev. Neurosci. |volume=22 |issue= 1-2 |pages= 68–73 |year= 2000 |pmid= 10657699 |doi=
*cite journal | author=Raatikainen-Ahokas A, Hytönen M, Tenhunen A, "et al." |title=BMP-4 affects the differentiation of metanephric mesenchyme and reveals an early anterior-posterior axis of the embryonic kidney. |journal=Dev. Dyn. |volume=217 |issue= 2 |pages= 146–58 |year= 2000 |pmid= 10706139 |doi= 10.1002/(SICI)1097-0177(200002)217:2<146::AID-DVDY2>3.0.CO;2-I |doilabel=10.1002/(SICI)1097-0177(200002)217:2146::AID-DVDY23.0.CO;2-I
*cite journal | author=van den Wijngaard A, Mulder WR, Dijkema R, "et al." |title=Antiestrogens specifically up-regulate bone morphogenetic protein-4 promoter activity in human osteoblastic cells. |journal=Mol. Endocrinol. |volume=14 |issue= 5 |pages= 623–33 |year= 2000 |pmid= 10809227 |doi=
*cite journal | author=Ying Y, Liu XM, Marble A, "et al." |title=Requirement of Bmp8b for the generation of primordial germ cells in the mouse. |journal=Mol. Endocrinol. |volume=14 |issue= 7 |pages= 1053–63 |year= 2000 |pmid= 10894154 |doi=
*cite journal | author=Nakade O, Takahashi K, Takuma T, "et al." |title=Effect of extracellular calcium on the gene expression of bone morphogenetic protein-2 and -4 of normal human bone cells. |journal=J. Bone Miner. Metab. |volume=19 |issue= 1 |pages= 13–9 |year= 2001 |pmid= 11156467 |doi=
*cite journal | author=Hatta T, Konishi H, Katoh E, "et al." |title=Identification of the ligand-binding site of the BMP type IA receptor for BMP-4. |journal=Biopolymers |volume=55 |issue= 5 |pages= 399–406 |year= 2001 |pmid= 11241215 |doi= 10.1002/1097-0282(2000)55:5<399::AID-BIP1014>3.0.CO;2-9 |doilabel=10.1002/1097-0282(2000)55:5399::AID-BIP10143.0.CO;2-9
*cite journal | author=Aoki H, Fujii M, Imamura T, "et al." |title=Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction. |journal=J. Cell. Sci. |volume=114 |issue= Pt 8 |pages= 1483–9 |year= 2001 |pmid= 11282024 |doi=

External links

* Online Mendelian Inheritance in Man link: OMIM|112262

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