Background: | Growth Differentiation Factor 11 (GDF-11), also known as BMP-11, is a member of the TGF-beta superfamily and is highly related to GDF-8. GDF-11 encodes a 407 amino acid (aa) prepropeptide which contains a signal sequence for secretion and an RXXR proteolytic processing site to yield a 109 aa residue carboxy-terminal mature protein. Mature GDF-11 contains the canonical 7-cysteine motif common to other TGF-beta superfamily members, however, like the TGF-beta s, Activins and GDF-8, GDF-11 also contains one extra pair of cysteine residues. At the amino acid sequence level, mature human, mouse, rat and chicken GDF-11 are 99-100% identical. As detected by in situ hybridization, GDF-11 is expressed in diverse regions of the mouse embryo: tailbud, somitic precursors, limbs, mandibular and branchial arches, dorsal neural tube, odontoblasts, nasal epithelium, and particular regions of the brain. Targeted deletion of GDF-11, in mice, results in a spectrum of abnormalities including palatal malformation, vertebral defects, elongated trunks with a reduced or absent tail, missing or malformed kidneys, and an increased number of neurons in the olfactory epithelium. GDF-11 signals through the Activin type II receptors and induces phosphorylation of Smad2 to mediate axial patterning. Systemic GDF-11 levels decline with age and administration of higher levels of GDF-11 can reverse age-related cardiac hypertrophy. In addition, systemic administration of recombinant GDF-11 protein restores genomic integrity and health of muscle stem cells, neurovasculature and enhances neurogenesis. |