Germ cell nuclear factor: An orphan receptor in search of a function

Germ Cell Nuclear Fatter (GCNF) is an orphan member of the nuclear receptor gene superfamily. Much has been understood about the functioning of GCNF w hich represents a candidate receptor for a novel hormonal signalling pathwa y. GCNF is nob closely related to other members of the nuclear receptor sup erfamily and forms its own branch within the superfamily tree. It has a uni que expression pattern that spans both embryonic and adult stages of develo pment. In the adult, it is expressed in the germ cells: oocytes and spermat ogenic cells as well as specific neuronal cells within the brain. In the em bryo, GCNF expression is turned on after gastrulation in all germ layers th e ectoderm, mesoderm and endoderm, An antero-posterior gradient of GCNF is established in the neuroectoderm of the embryo, suggesting a role in regula tion of neuronal and germ cell development, Regulation of physiological pro cesses by a nuclear receptor is achieved through regulation of gene express ion. GCNF is the only nuclear receptor to specifically bind to DRO hormone response elements to regulate gene expression. In the absense of a ligand, GCNF represses gene expression. GCNF is capable of regulating the expressio n of the protamine genes in a response element-dependent manner. At present the ligand for GCNF is unknown, but it is hypothesized that GCNF is a rece ptor for a novel hormonal signalling pathway that effects its biological re sponse by regulating the expression of a subset of genes containing DRO res ponse elements.