Background:

Bone morphogenetic protein 4 (BMP4) belongs to the TGF-β superfamily of proteins. Like other bone morphogenetic proteins, it is involved in bone and cartilage development. It is mainly involved in tooth and limb development, fracture repair, 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. Recombinant human BMP-4, expressed in HeLa cells, is a 31-36 kDa homodimeric glycoprotein.

BMP-4 and BMP-7 are each 98% conserved between human and mouse. Human BMP-4 shares 85% aa sequence identity with human BMP-2 and less than 50% aa sequence identity with other BMPs. Human BMP-7 shares approximately 60 - 70% aa sequence identity with BMP-5, -6, and -8 and less than 50% aa sequence identity with other BMPs.