Bone morphogenetic protein 4

Bone morphogenetic protein 4 is a protein that in humans is encoded by BMP4 gene. BMP4 is found on chromosome 14q22-q23.

BMP4 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. BMP4 is highly conserved evolutionarily. BMP4 is found in early embryonic development in the ventral marginal zone and in the eye, heart blood and otic vesicle.

Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site.

Alternative splicing in the 5' untranslated region of this gene has been described and three variants are described, all encoding an identical protein.

Yielding an active carboxy-terminal peptide of 116 residues, human bmp4 is initially synthesized as a forty percent residue preproprotein which is cleaved post translationally. BMP4 has seven residues which are conserved and glycosylated. The monomers are held with disulphide bridges and 3 pairs of cysteine amino acids. This conformation is called a "cystine knot". BMP4 can form homodimers or heterodimers with similar BMPS. One example of this is BMP7. This ability to form homodimers or heterodimers gives the ability to have greater osteoinductive activity than just bmp4 alone. Not much is known yet about how BMPS interact with the extracellular matrix. As well little is known about the pathways which then degrade BMP4.

BMP4 is a polypeptide belonging to the TGF-β superfamily of proteins. Like other bone morphogenetic proteins (BMPs), it is critical for bone and cartilage development, including roles in tooth and limb formation and fracture repair. BMP4 is particularly important for initiating endochondral ossification in humans, and is also involved in muscle development, bone mineralization, and ureteric bud formation. It stimulates differentiation of ectodermal tissue, and drives osteoblastic differentiation of mesenchymal stem cells.^{[citation needed]}

During embryogenesis, BMP4 is essential for dorsal–ventral axis specification and mesoderm patterning. In Xenopus, BMP4 induces ventral mesoderm and suppresses neural fate by promoting epidermal differentiation. In mice, loss of BMP4 results in impaired mesoderm formation.

BMP4 plays a dorsalizing role in neural tube patterning, acting with BMP7 from the roof plate to specify dorsal interneurons and counteract Sonic hedgehog (Shh) signaling from the floor plate. It also contributes to neural crest cell apoptosis in the hindbrain region.