Expression and putative function of kisspeptins and their receptors during early development in medaka

Kisspeptins (Kiss1 and Kiss2) and their receptors (putatively Gpr54-1 and Gpr54-2) have emerged as key players in vertebrate reproduction owing to their stimulatory effect on the hypothalamus-pituitary-gonadal axis. Virtually nothing is known, however, about their role during embryogenesis. Using medaka (Teleostei) as model system, we report for the first time in vertebrates, an early developmental expression and putative function of kisspeptins. Expression analyses and knockdown experiments suggest that early actions of kisspeptins are probably mediated by binding to maternally supplied Gpr54-1 and late action by both Gpr54-1 and Gpr54-2. Knockdown of maternally provided kiss1 and gpr54-1 arrested development during gastrulation, before establishment of any germ layers, while knockdown of zygotically provided kiss1 and gpr54-1 disrupted brain development. A similar phenotype was observed for gpr54-2 knockdown embryos, suggesting a critical role for kiss1, gpr54-1, and gpr54-2 in neurulation. These data demonstrate that kisspeptin signaling is active both maternally and zygotically, and is involved in embryonic survival and morphogenesis.