The recent discoveries of the kisspeptin system and its involvement in reproduction have been major breakthroughs in neuroendocrinology. In zebrafish, two kisspeptins (Kiss1 and Kiss2) and two kisspeptins receptors (GPR54.1 = Kiss1r and GPR54.2 = Kiss2r) are expressed and each of them is encoded by a single gene. Recently, we have fully described the distribution of the kisspeptins and their receptors in the brain of adult zebrafish. Kiss2 expressing neurons are mostly localized in the dorsal and ventral hypothalamus. They project widely in the midbrain and anterior brain in regions expressing the Kiss2r and are likely in contact with GnRH3 fibers. In contrast, Kiss1 expressing neurons are exclusively localized in the habenula, which also expresses the Kiss1r, and project in the interpeduncular and raphe nuclei. These results suggest a gene speciation in zebrafish, with the Kiss2 system involved in reproductive processes and the Kiss1 system in interactions with others processes like food intake or environmental perception. Interestingly, exposure of juvenile zebrafish to estrogens up-regulates the kiss2 gene, suggesting that the Kiss2 system could mediate the neuroendocrine control of reproduction by estrogens. In order to study (i) the kiss2 expression in early development and (ii) the modulation of this expression in response to estrogens, we developed a transgenic zebrafish line, zftg(kiss2-GFP), expressing GFP under the control of the zebrafish kiss2 promoter. This zebrafish transgenic line, validated by immunohistochemistry, expresses GFP as early as 4 dpf in the hypothalamus, demonstrating that the kiss2 system is functional widely before sexual maturation. Moreover, exposure of zebrafish embryos to estrogens enhances the number of Kiss2 immunoreactive-fibers, suggesting that estrogens modulate the development of kiss2 neurons. Taken together, these results reinforce the view that, in zebrafish, kiss2 is probably linked to the regulation of reproductive processes. Moreover, the zftg(kiss2-GFP) line appears to be a promising tool to study the role of Kiss2 in early development, notably its interaction with the GnRH system, but also its potential disruption by environmental estrogenic compounds.
