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.
Glial Cell Line-Derived Neurotrophic Factor (GDNF) is a disulfide-linked homodimeric glycoprotein that belongs to the TGF-β superfamily. It has been shown to promote the survival of various neuronal subpopulations in both the central as well as the peripheral nervous systems at different stages of their development. Human GDNF cDNA encodes a 211 amino acid residue prepropeptide that is processed to yield a dimeric protein. Mature human GDNF was predicted to contain two 134 amino acid residue subunits. Cells known to express GDNF include Sertoli cells, type 1 astrocytes, Schwann cells, neurons, pinealocytes and skeletal muscle cells. Mutations in this gene may be associated with Hirschsprung disease.
Glial Fibrillary Acidic Protein (GFAP) is an intermediate filament (IF) protein which belongs to the intermediate filament family. GFAP is expressed in numerous cell types of the central nervous system (CNS), ependymal cells and phosphorylated by PKN1. GFAP, a class-III intermediate filament, is a cell-specific marker during the development of the central nervous system and distinguishes astrocytes from other glial cells. It is closely related to its non-epithelial family members, vimentin, desmin, and peripherin, which are all involved in the structure and function of the cell’s cytoskeleton. GFAP is thought to help to maintain astrocyte mechanical strength, as well as the shape of cells but its exact function remains poorly understood.
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