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.
Discovery
Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site.
Function
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. This particular family member plays an important role in the onset of endochondral bone formation in humans. It has been shown to be involved in muscle development, bone mineralization, and ureteric bud development.
BMP4 stimulates differentiation of overlying ectodermal tissue.
Bone morphogenetic proteins are known to stimulate bone formation in adult animals. This is thought that inducing osteoblastic commitment and differentiation of stem cells such as mesenchymal stem cells.BMPs are known to play a large role in embryonic development. In the embryo BMP4 helps establish dorsal-ventral axis formation in Xenopus frog through inducing ventral mesoderm. In mice targeted inactivation of BMP4 disrupts mesoderm from forming. As well establishes dorsal-ventral patterning of the developing neural tube with the help of BMP7, and inducing dorsal characters.
BMP4 also limits the extent to which neural differentiation in Xenopus embryos occurs by inducing epidermis formation rather than neural tissue. They can aid in inducing the lateral characteristics in somites. Somites are required for the development of cartilage, bone, dermis on the dorsal side of the body, thoracic muscles and muscles within limbs. BMP4 helps in the patterning of the developing head though inducing apoptosis of the neural crest cells; this is done in the hindbrain.
In adult, BMP4 is important for the neurogenesis (i.e., the generation of new neurons) that occurs throughout life in two neurogenic niches of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ) adjacent to lateral ventricles. In these niches new neurons are continuously generated from stem cells. In fact it has been shown that in the dentate gyrus BMP4 maintains neural stem cells in quiescence, thus preventing the depletion of the pool of stem cells. In the SVZ , BMP-mediated signaling via Smad4 is required to initiate neurogenesis from adult neural stem cells and suppress the alternative fate of oligodendrogliogenesis. Moreover, it has been shown that in the SVZ BMP4 has a prodifferentiative effect, since it rescues a defect of terminal differentiation in SVZ neurospheres where the gene Tis21/BTG2 - required for terminal differentiation - has been deleted. Tis21 is a positive regulator of BMP4 expression in the SVZ.
BMP4 is important for bone and cartilage metabolism. The BMP4 signaling has been found in formation of early mesoderm and germ cells. Limb bud regulation and development of the lungs, liver, teeth and facial mesenchyme cells are other important functions attributed to BMP4 signaling. Digit formation is influenced by BMP4, along with other BMP signals. The interdigital mesenchyme exhibits BMP4, which prevents apoptosis of the region. Tooth formation relies on BMP4 expression, which induces Msx 1 and 2. These transcription factors turn the forming tooth to become and incisor.
BMP4 also plays important roles in adipose tissue: it is essential for white adipogenesis, and promotes adipocyte differentiation. Additionally, it is also important for brown fat, where it induces UCP1, related to non-shivering thermogenesis.
BMP4 secretion helps cause differentiation of the ureteric bud into the ureter.
BMP4 antagonizes organizer tissue and is expressed in early development in ectoderm and mesoderm tissue. Upon gastrulation, the transcription of BMP4 is limited to the ventrolateral marginal zone due to inhibition from the dorsalizing side of the developing embryo. BMP4 aids in ventralizing mesoderm, which guides the dorsal-ventral axis formation. In Xenopus BMP4 has been found to aid in formation of blood and blood islands.