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Hodne K.,Weltzien Laboratory | Hodne K.,University of Oslo | Hodne K.,University of Tokyo | Weltzien F.-A.,Weltzien Laboratory | And 3 more authors.
Endocrinology | Year: 2013

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 brain-pituitarygonadal axis. Virtually nothing is known, however, about their role during embryogenesis. Using medaka (Teleostei) as a 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, whereas 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.


Weltzien F.-A.,Weltzien Laboratory | Weltzien F.-A.,University of Oslo | Hildahl J.,Weltzien Laboratory | Hildahl J.,University of Oslo | And 4 more authors.
Molecular and Cellular Endocrinology | Year: 2014

Pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are key regulators of vertebrate reproduction. The differential regulation of these hormones, however, is poorly understood and little is known about gonadotrope embryonic development. The different cell types in the vertebrate pituitary develop from common progenitor cells just after gastrulation. Proper development and merging of the anterior and posterior pituitary is dependent upon carefully regulated cell-to-cell interactions, and a suite of signaling pathways with precisely organized temporal and spatial expression patterns, which include transcription factors and their co-activators and repressors. Among the pituitary endocrine cell types, the gonadotropes are the last to develop and become functional. Although much progress has been made during the last decade regarding details of gonadotrope development, the coordinated program for their maturation is not well described.FSH and LH form an integral part of the hypothalamo-pituitary-gonad axis, the main regulator of gonad development and reproduction. Besides regulating gonad development, pre- and early post-natal activity in this axis is thought to be essential for proper development, especially of the central nervous system in mammals. As a means to investigate early functions of FSH and LH in more detail, we have developed a stable transgenic line of medaka with the LH beta subunit gene (lhb) promoter driving green fluorescent protein (Gfp) expression to characterize development of lhb-expressing gonadotropes. The lhb gene is maternally expressed early during embryogenesis. lhb-Expressing cells are initially localized outside the primordial pituitary in the developing gut tube as early as 32. hpf. At hatching, lhb-Gfp is clearly detected in the gut epithelium and in the anterior digestive tract. lhb-Gfp expression later consolidates in the developing pituitary by 2. weeks post-fertilization. This review discusses status of knowledge regarding pituitary morphology and development, with emphasis on gonadotrope cells and gonadotropins during early development, comparing main model species like mouse, zebrafish and medaka, including possible developmental functions of the observed extra pituitary expression of lhb in medaka. © 2013 Elsevier Ireland Ltd.


PubMed | Weltzien Laboratory
Type: Journal Article | Journal: Endocrinology | Year: 2013

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 brain-pituitary-gonadal axis. Virtually nothing is known, however, about their role during embryogenesis. Using medaka (Teleostei) as a 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, whereas 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.

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