Germ Cell Nuclear Factor: An Orphan Receptor in Search of a Function

Abstract

Germ Cell Nuclear Factor (GCNF) is an orphan member of the nuclear receptor gene superfamily. Much has been understood about the functioning of GCNF which represents a candidate receptor for a novel hormonal signalling pathway. GCNF is not closely related to other members of the nuclear receptor superfamily and forms its own branch within the superfamily tree. It has a unique expression pattern that spans both embryonic and adult stages of development. In the adult, it is expressed in the germ cells: oocytes and spermatogenic cells as well as specific neuronal cells within the brain. In the embryo, GCNF expression is turned on after gastrulation in all germ layers the ectoderm, mesoderm and endoderm. An antero-posterior gradient of GCNF is established in the neuroectoderm of the embryo, suggesting a role in regulation of neuronal and germ cell development. Regulation of physiological processes by a nuclear receptor is achieved through regulation of gene expression. GCNF is the only nuclear receptor to specifcally bind to DR0 hormone response elements to regulate gene expression. In the absense of a ligand, GCNF represses gene expression. GCNF is capable of regulating the expression 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 receptor for a novel hormonal signalling pathway that effects its biological response by regulating the expression of a subset of genes containing DR0 response elements.