Abstract
Kisspeptin is a hypothalamic neuropeptide, which acts directly on gonadotropin-releasing hormone (GnRH)-secreting neurons via its cognate receptor (GPR54 or Kiss-R) to stimulate GnRH secretion in mammals. In non-mammalian vertebrates, there are multiple kisspeptins (Kiss1 and Kiss2) and Kiss-R types. Recent gene knockout studies have demonstrated that fish kisspeptin systems are not essential in the regulation of reproduction. Studying the detailed distribution of kisspeptin receptor in the brain and pituitary is important for understanding the multiple action sites and potential functions of the kisspeptin system. In the present study, we generated a specific antibody against zebrafish Kiss2-R (=Kiss1Ra/GPR54-1/Kiss-R2/KissR3) and examined its distribution in the brain and pituitary. Kiss2-R-immunoreactive cell bodies are widely distributed in the brain including in the dorsal telencephalon, preoptic area, hypothalamus, optic tectum, and in the hindbrain regions. Double-labeling showed that not all but a subset of preoptic GnRH3 neurons expresses Kiss2-R, while Kiss2-R is expressed in most of the olfactory GnRH3 neurons. In the posterior preoptic region, Kiss2-R immunoreactivity was seen in vasotocin cells. In the pituitary, Kiss2-R immunoreactivity was seen in corticotropes, but not in gonadotropes. The results in this study suggest that Kiss2 and Kiss2-R signaling directly serve non-reproductive functions and indirectly subserve reproductive functions in teleosts.
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References
Abe H, Oka Y (2006) Neuromodulatory functions of terminal nerve-GnRH neurons. Fish Physiology 25:455–503
Abraham E, Palevitch O, Gothilf Y, Zohar Y (2010) Targeted gonadotropin-releasing hormone-3 neuron ablation in zebrafish: effects on neurogenesis, neuronal migration, and reproduction. Endocrinology 151:332–340
Abraham E, Palevitch O, Ijiri S, Du SJ, Gothilf Y, Zohar Y (2008) Early development of forebrain gonadotrophin-releasing hormone (GnRH) neurones and the role of GnRH as an autocrine migration factor. J Neuroendocrinol 20:394–405
Agetsuma M, Aizawa H, Aoki T, Nakayama R, Takahoko M, Goto M, Sassa T, Amo R, Shiraki T, Kawakami K, Hosoya T, Higashijima S, Okamoto H (2010) The habenula is crucial for experience-dependent modification of fear responses in zebrafish. Nat Neurosci 13:1354–1356
Backholer K, Smith JT, Rao A, Pereira A, Iqbal J, Ogawa S, Li Q, Clarke IJ (2010) Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells. Endocrinology 151:2233–2243
Bae Y-K, Kani S, Shimizu T, Tanabe K, Nojima H, Kimura Y, Higashijima S-I, Hibi M (2009) Anatomy of zebrafish cerebellum and screen for mutations affecting its development. Dev Biol 330:406–426
Beck BH, Fuller SA, Peatman E, McEntire ME, Darwish A, Freeman DW (2012) Chronic exogenous kisspeptin administration accelerates gonadal development in basses of the genus Morone. Comp Biochem Physiol A Mol Integr Physiol 162:265–273
Chang JP, Mar A, Wlasichuk M, Wong AOL (2012) Kisspeptin-1 directly stimulates LH and GH secretion from goldfish pituitary cells in a Ca2+-dependent manner. Gen Comp Endocrinol 179:38–46
Comninos AN, Anastasovska J, Sahuri-Arisoylu M, Li X, Li S, Hu M, Jayasena CN, Ghatei MA, Bloom SR, Matthews PM (2016) Kisspeptin signaling in the amygdala modulates reproductive hormone secretion. Brain Struct Funct 221:2035–2047
Comninos AN, Dhillo WS (2018) Emerging roles of kisspeptin in sexual and emotional brain processing. Neuroendocrinology 106:195–202
D’Anglemont de Tassigny X, Fagg LA, Carlton MBL, Colledge WH (2008) Kisspeptin can stimulate gonadotropin-releasing hormone (GnRH) release by a direct action at GnRH nerve terminals. Endocrinology 149:3926–3932
Delgado L, Schmachtenberg O (2008) Immunohistochemical localization of GABA, GAD65, and the receptor subunits GABA Aα1 and GABA B1 in the zebrafish cerebellum. Cerebellum 7:444–450
Dungan HM, Clifton DK, Steiner RA (2006) Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion. Endocrinology 147:1154–1158
Escobar S, Servili A, Espigares F, Gueguen M-M, Brocal I, Felip A, Gómez A, Carrillo M, Zanuy S, Kah O (2013) Expression of kisspeptins and kiss receptors suggests a large range of functions for kisspeptin systems in the brain of the European sea bass. PLoS One 8:e70177
Espigares F, Zanuy S, Gómez A (2015) Kiss2 as a regulator of Lh and Fsh secretion via paracrine/autocrine signaling in the teleost fish European sea bass (Dicentrarchus labrax). Biol Reprod 93:1–12
Felip A, Zanuy S, Pineda R, Pinilla L, Carrillo M, Tena-Sempere M, Gomez A (2009) Evidence for two distinct KiSS genes in non-placental vertebrates that encode kisspeptins with different gonadotropin-releasing activities in fish and mammals. Mol Cell Endocrinol 312:61–71
Freeman WJ (2005) NDN, volume transmission, and self-organization in brain dynamics. J Integr Neurosci 4:407–421
Fu L-Y, van den Pol AN (2010) Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism. J Neurosci 30:10205–10219
Gopinath A, Andrew TL, Whitlock KE (2004) Temporal and spatial expression of gonadotropin releasing hormone (GnRH) in the brain of developing zebrafish (Danio rerio). Gene Expr Patterns 4:65–70
Gopurappilly R, Ogawa S, Parhar IS (2013) Functional significance of GnRH and kisspeptin, and their cognate receptors in teleost reproduction. Front Endocrinol 4:24
Grone BP, Maruska KP, Korzan WJ, Fernald RD (2010) Social status regulates kisspeptin receptor mRNA in the brain of Astatotilapia burtoni. Gen Comp Endocrinol 169:98–107
Herbison AE, D’Anglemont de Tassigny X, Doran J, Colledge WH (2010) Distribution and postnatal development of Gpr54 gene expression in mouse brain and gonadotropin-releasing hormone neurons. Endocrinology 151:312–321
Herkenham M (1987) Mismatches between neurotransmitter and receptor localizations in brain: observations and implications. Neuroscience 23:1–38
Higo S, Honda S, Iijima N, Ozawa H (2016) Mapping of kisspeptin receptor mRNA in the whole rat brain and its co-localisation with oxytocin in the paraventricular nucleus. J Neuroendocrinol 28
Kanda S, Akazome Y, Matsunaga T, Yamamoto N, Yamada S, Tsukamura H, Maeda K, Oka Y (2008) Identification of KiSS-1 product kisspeptin and steroid-sensitive sexually dimorphic kisspeptin neurons in medaka (Oryzias latipes). Endocrinology 149:2467–2476
Kanda S, Akazome Y, Mitani Y, Okubo K, Oka Y (2013) Neuroanatomical evidence that kisspeptin directly regulates isotocin and vasotocin neurons. PLoS One 8:e62776
Keen KL, Wegner FH, Bloom SR, Ghatei MA, Terasawa E (2008) An increase in kisspeptin-54 release occurs with the pubertal increase in luteinizing hormone-releasing hormone-1 release in the stalk-median eminence of female rhesus monkeys in vivo. Endocrinology 149:4151–4157
Kim NN, Choi Y-U, Park H-S, Choi CY (2015) Kisspeptin regulates the somatic growth-related factors of the cinnamon clownfish Amphiprion melanopus. Comp Biochem Physiol A Mol Integr Physiol 179:17–24
Kitahashi T, Ogawa S, Parhar IS (2009) Cloning and expression of kiss2 in the zebrafish and medaka. Endocrinology 150:821–831
Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden J, Le Poul E, Brezillon S, Tyldesley R, Suarez-Huerta N, Vandeput F (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276:34631–34636
Lal P, Tanabe H, Suster ML, Ailani D, Kotani Y, Muto A, Itoh M, Iwasaki M, Wada H, Yaksi E (2018) Identification of a neuronal population in the telencephalon essential for fear conditioning in zebrafish. BMC Biol 16:45
Larson E, O'Malley D, Melloni R (2006) Aggression and vasotocin are associated with dominant-subordinate relationships in zebrafish. Behav Brain Res 167:94–102
Lee A, Mathuru AS, Teh C, Kibat C, Korzh V, Penney TB, Jesuthasan S (2010) The habenula prevents helpless behavior in larval zebrafish. Curr Biol 20:2211–2216
Lee YR, Tsunekawa K, Moon MJ, Um HN, Hwang JI, Osugi T, Otaki N, Sunakawa Y, Kim K, Vaudry H, Kwon HB, Seong JY, Tsutsui K (2009) Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. Endocrinology 150:2837–2846
Li S, Zhang Y, Liu Y, Huang X, Huang W, Lu D, Zhu P, Shi Y, Cheng CH, Liu X, Lin H (2009) Structural and functional multiplicity of the kisspeptin/GPR54 system in goldfish (Carassius auratus). J Endocrinol 201:407–418
Liu N-A, Huang H, Yang Z, Herzog W, Hammerschmidt M, Lin S, Melmed S (2003) Pituitary corticotroph ontogeny and regulation in transgenic zebrafish. Mol Endocrinol 17:959–966
Liu Q, Bhattarai S, Wang N, Sochacka-Marlowe A (2015) Differential expression of protocadherin-19, protocadherin-17, and cadherin-6 in adult zebrafish brain. J Comp Neurol 523:1419–1442
Liu Y, Tang H, Xie R, Li S, Liu X, Lin H, Zhang Y, Cheng CH (2017) Genetic evidence for multifactorial control of the reproductive axis in zebrafish. Endocrinology 158:604–611
Luque RM, Córdoba-Chacón J, Gahete MD, Navarro VM, Tena-Sempere M, Kineman RD, Castaño JP (2011) Kisspeptin regulates gonadotroph and somatotroph function in nonhuman primate pituitary via common and distinct signaling mechanisms. Endocrinology 152:957–966
Martel J-C, St-Pierre S, Quirion R (1986) Neuropeptide Y receptors in rat brain: autoradiographic localization. Peptides 7:55–60
Marvel M, Spicer OS, Wong T-T, Zmora N, Zohar Y (2018) Knockout of the Gnrh genes in zebrafish: effects on reproduction and potential compensation by reproductive and feeding-related neuropeptides. Biol Reprod 99:565–577
Mechaly AS, Tovar-Bohórquez M, Mechaly AE, Suku E, Giorgetti A, Pérez M, Ortí G, Viñas J, Somoza GM (2018) Evidences of alternative splicing as a regulatory mechanism for Kissr2 in pejerrey fish. Front Endocrinol 9:604
Meek J (1983) Functional anatomy of the tectum mesencephali of the goldfish. An explorative analysis of the functional implications of the laminar structural organization of the tectum. Brain Res Rev 6:247–297
Mitani Y, Kanda S, Akazome Y, Zempo B, Oka Y (2010) Hypothalamic Kiss1 but not Kiss2 neurons are involved in estrogen feedback in medaka (Oryzias latipes). Endocrinology 151:1751–1759
Mueller T, Dong Z, Berberoglu MA, Guo S (2011) The dorsal pallium in zebrafish, Danio rerio (Cyprinidae, Teleostei). Brain Res 1381:95–105
Mueller T, Guo S (2009) The distribution of GAD67-mRNA in the adult zebrafish (teleost) forebrain reveals a prosomeric pattern and suggests previously unidentified homologies to tetrapods. J Comp Neurol 516:553–568
Mueller T, Vernier P, Wullimann MF (2004) The adult central nervous cholinergic system of a neurogenetic model animal, the zebrafish Danio rerio. Brain Res 1011:156–169
Nakajo M, Kanda S, Karigo T, Takahashi A, Akazome Y, Uenoyama Y, Kobayashi M, Oka Y (2018) Evolutionally conserved function of kisspeptin neuronal system is nonreproductive regulation as revealed by nonmammalian study. Endocrinology 159:163–183
Nathan FM, Ogawa S, Parhar IS (2015) Neuronal connectivity between habenular glutamate-kisspeptin1 co-expressing neurons and the raphe 5-HT system. J Neurochem 135:814–829
Nocillado J, Biran J, Lee Y, Levavi-Sivan B, Mechaly AS, Zohar Y, Elizur A (2012) The Kiss2 receptor (Kiss2r) gene in Southern Bluefin Tuna, Thunnus maccoyii and in Yellowtail Kingfish, Seriola lalandi–functional analysis and isolation of transcript variants. Mol Cell Endocrinol 362:211–220
Oehlmann VD, Korte H, Sterner C, Korsching SI (2002) A neuropeptide FF-related gene is expressed selectively in neurons of the terminal nerve in Danio rerio. Mech Dev 117:357–361
Ogawa S, Akiyama G, Kato S, Soga T, Sakuma Y, Parhar IS (2006) Immunoneutralization of gonadotropin-releasing hormone type-III suppresses male reproductive behavior of cichlids. Neurosci Lett 403:201–205
Ogawa S, Nathan FM, Parhar IS (2014) Habenular kisspeptin modulates fear in the zebrafish. Proc Natl Acad Sci U S A 111:3841–3846
Ogawa S, Ng KW, Ramadasan PN, Nathan FM, Parhar IS (2012) Habenular Kiss1 neurons modulate the serotonergic system in the brain of zebrafish. Endocrinology 153:2398–2407
Ogawa S, Ng KW, Xue X, Ramadasan PN, Sivalingam M, Li S, Levavi-Sivan B, Lin H, Liu X, Parhar IS (2013) Thyroid hormone upregulates hypothalamic kiss2 gene in the male Nile tilapia, Oreochromis niloticus. Front Endocrinol 4:184
Ogawa S, Parhar IS (2013) Anatomy of the kisspeptin systems in teleosts. Gen Comp Endocrinol 181:169–174
Ogawa S, Parhar IS (2018) Biological significance of kisspeptin–kiss 1 receptor signaling in the habenula of teleost species. Front Endocrinol 9:222
Ogawa S, Sivalingam M, Biran J, Golan M, Anthonysamy RS, Levavi-Sivan B, Parhar IS (2016) Distribution of LPXRFa, a gonadotropin-inhibitory hormone ortholog peptide, and LPXRFa receptor in the brain and pituitary of the tilapia. J Comp Neurol 524:2753–2775
Ohga H, Selvaraj S, Adachi H, Imanaga Y, Nyuji M, Yamaguchi A, Matsuyama M (2014) Functional analysis of kisspeptin peptides in adult immature chub mackerel (Scomber japonicus) using an intracerebroventricular administration method. Neurosci Lett 561:203–207
Oka Y (2009) Three types of gonadotrophin-releasing hormone neurones and steroid-sensitive sexually dimorphic kisspeptin neurones in teleosts. J Neuroendocrinol 21:334–338
Parhar I, Ogawa S, Kitahashi T (2012) RFamide peptides as mediators in environmental control of GnRH neurons. Prog Neurobiol 98:176–196
Parhar IS (2002) Cell migration and evolutionary significance of GnRH subtypes. Prog Brain Res 141:3–17
Parhar IS, Ogawa S, Sakuma Y (2004) Laser-captured single digoxigenin-labeled neurons of gonadotropin-releasing hormone types reveal a novel G protein-coupled receptor (Gpr54) during maturation in cichlid fish. Endocrinology 145:3613–3618
Park MK, Wakabayashi K (1986) Preparation of a monoclonal antibody to common amino acid sequence of LHRH and its application. Endocrinol Jpn 33:257–272
Pasquier J, Kamech N, Lafont A-G, Vaudry H, Rousseau K, Dufour S (2014) Molecular evolution of GPCRs: Kisspeptin/kisspeptin receptors. J Mol Endocrinol 52:T101–T117
Pasquier J, Lafont AG, Leprince J, Vaudry H, Rousseau K, Dufour S (2011) First evidence for a direct inhibitory effect of kisspeptins on LH expression in the eel, Anguilla anguilla. Gen Comp Endocrinol 173:216–225
Pert CB, Ruff MR, Weber RJ, Herkenham M (1985) Neuropeptides and their receptors: a psychosomatic network. J Immunol 135:820S–826S
Peter RE, Yu KL, Marchant TA, Rosenblum PM (1990) Direct neural regulation of the teleost adenohypophysis. J Exp Zool 256:84–89
Ramakrishnan S, Lee W, Navarre S, Kozlowski DJ, Wayne NL (2010) Acquisition of spontaneous electrical activity during embryonic development of gonadotropin-releasing hormone-3 neurons located in the terminal nerve of transgenic zebrafish (Danio rerio). Gen Comp Endocrinol 168:401–407
Ramaswamy S, Guerriero KA, Gibbs RB, Plant TM (2008) Structural interactions between kisspeptin and GnRH neurons in the mediobasal hypothalamus of the male rhesus monkey (Macaca mulatta) as revealed by double immunofluorescence and confocal microscopy. Endocrinology 149:4387–4395
Rao YS, Mott NN, Pak TR (2011) Effects of kisspeptin on parameters of the HPA axis. Endocrine 39:220–228
Rink E, Wullimann MF (2001) The teleostean (zebrafish) dopaminergic system ascending to the subpallium (striatum) is located in the basal diencephalon (posterior tuberculum). Brain Res 889:316–330
Selvaraj S, Ohga H, Kitano H, Nyuji M, Yamaguchi A, Matsuyama M (2013) Peripheral administration of Kiss1 pentadecapeptide induces gonadal development in sexually immature adult scombroid fish. Zool Sci 30:446–454
Semsar K, Kandel F, Godwin J (2001) Manipulations of the AVT system shift social status and related courtship and aggressive behaviour in the bluehead wrasse. Horm Behav 40:21–31
Servili A, Le Page Y, Leprince J, Caraty A, Escobar S, Parhar IS, Seong JY, Vaudry H, Kah O (2011) Organization of two independent kisspeptin systems derived from evolutionary-ancient kiss genes in the brain of zebrafish. Endocrinology 152:1527–1540
Shahjahan M, Motohashi E, Doi H, Ando H (2010) Elevation of Kiss2 and its receptor gene expression in the brain and pituitary of grass puffer during the spawning season. Gen Comp Endocrinol 169:48–57
Soga T, Ogawa S, Millar RP, Sakuma Y, Parhar IS (2005) Localization of the three GnRH types and GnRH receptors in the brain of a cichlid fish: insights into their neuroendocrine and neuromodulator functions. J Comp Neurol 487:28–41
Song Y, Duan X, Chen J, Huang W, Zhu Z, Hu W (2015) The distribution of kisspeptin (Kiss)1- and Kiss2-positive neurones and their connections with gonadotrophin-releasing hormone-3 neurones in the zebrafish brain. J Neuroendocrinol 27:198–211
Spicer OS, Wong T-T, Zmora N, Zohar Y (2016) Targeted mutagenesis of the hypophysiotropic Gnrh3 in zebrafish (Danio rerio) reveals no effects on reproductive performance. PLoS One 11:e0158141
Steven C, Lehnen N, Kight K, Ijiri S, Klenke U, Harris WA, Zohar Y (2003) Molecular characterization of the GnRH system in zebrafish (Danio rerio): cloning of chicken GnRH-II, adult brain expression patterns and pituitary content of salmon GnRH and chicken GnRH-II. Gen Comp Endocrinol 133:27–37
Takahashi A, Kanda S, Abe T, Oka Y (2016) Evolution of the hypothalamic-pituitary-gonadal axis regulation in vertebrates revealed by knockout medaka. Endocrinology 157:3994–4002
Tang H, Liu Y, Luo D, Ogawa S, Yin Y, Li S, Zhang Y, Hu W, Parhar IS, Lin H, Liu X, Cheng CHK (2015) The kiss/kissr systems are dispensable for zebrafish reproduction: evidence from gene knockout studies. Endocrinology 156:589–599
Thompson RR, Walton JC (2004) Peptide effects on social behavior: effects of vasotocin and isotocin on social approach behavior in male goldfish (Carassius auratus). Behav Neurosci 118:620
Trudeau VL (2018) Facing the challenges of neuropeptide gene knockouts: why do they not inhibit reproduction in adult teleost fish? Front Neurosci 12:302
van Aerle R, Kille P, Lange A, Tyler CR (2008) Evidence for the existence of a functional Kiss1/Kiss1 receptor pathway in fish. Peptides 29:57–64
Van Pett K, Viau V, Bittencourt JC, Chan RK, Li HY, Arias C, Prins GS, Perrin M, Vale W, Sawchenko PE (2000) Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse. J Comp Neurol 428:191–212
van den Pol AN (2012) Neuropeptide transmission in brain circuits. Neuron 76:98–115
Wang B, Yang G, Liu Q, Qin J, Xu Y, Li W, Liu X, Shi B (2017) Inhibitory action of tongue sole LPXRFa, the piscine ortholog of gonadotropin-inhibitory hormone, on the signaling pathway induced by tongue sole kisspeptin in COS-7 cells transfected with their cognate receptors. Peptides 95:62–67
Wang B, Yang G, Xu Y, Li W, Liu X (2019) Recent studies of LPXRFa receptor signaling in fish and other vertebrates. Gen Comp Endocrinol 277:3–8
Wang Q, Sham KWY, Ogawa S, Li S, Parhar IS, Cheng CHK, Liu X, Lin H (2013) Regulation of the two kiss promoters in goldfish (Carassius auratus) by estrogen via different ERα pathways. Mol Cell Endocrinol 375:130–139
Whitlock KE, Smith KM, Kim H, Harden MV (2005) A role for foxd3 and sox10 in the differentiation of gonadotropin-releasing hormone (GnRH) cells in the zebrafish Danio rerio. Development 132:5491–5502
Wullimann MF, Rupp B, Reichert H (1996) Neuroanatomy of the zebrafish brain: a topologocal atlas. Birkhauser, Berlin
Xia W, Smith O, Zmora N, Xu S, Zohar Y (2014) Comprehensive analysis of GnRH2 neuronal projections in zebrafish. Sci Rep 4:3676
Yamamoto N, Oka Y, Kawashima S (1997) Lesions of gonadotropin-releasing hormone-immunoreactive terminal nerve cells: effects on the reproductive behavior of male dwarf gouramis. Neuroendocrinology 65:403–412
Yang B, Jiang Q, Chan T, Ko WK, Wong AO (2010) Goldfish kisspeptin: molecular cloning, tissue distribution of transcript expression, and stimulatory effects on prolactin, growth hormone and luteinizing hormone secretion and gene expression via direct actions at the pituitary level. Gen Comp Endocrinol 165:60–71
Zhang Y, Li S, Liu Y, Lu D, Chen H, Huang X, Liu X, Meng Z, Lin H, Cheng CHK (2010) Structural diversity of the GnIH/GnIH receptor system in teleost: its involvement in early development and the negative control of LH release. Peptides 31:1034–1043
Zhao Y, Lin M-CA, Mock A, Yang M, Wayne NL (2014) Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio). PLoS One 9:e104330
Zmora N, Stubblefield J, Golan M, Servili A, Levavi-Sivan B, Zohar Y (2014) The medio-basal hypothalamus as a dynamic and plastic reproduction-related kisspeptin-gnrh-pituitary center in fish. Endocrinology 155:1874–1886
Zmora N, Stubblefield J, Zulperi Z, Biran J, Levavi-Sivan B, Muñoz-Cueto J-A, Zohar Y (2012) Differential and gonad stage-dependent roles of kisspeptin1 and kisspeptin2 in reproduction in the modern teleosts, Morone species. Biol Reprod 86:177
Zmora N, Stubblefield JD, Wong T-T, Levavi-Sivan B, Millar RP, Zohar Y (2015) Kisspeptin antagonists reveal kisspeptin 1 and kisspeptin 2 differential regulation of reproduction in the teleost, Morone saxatilis. Biol Reprod 93(76):71–12
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This work was supported by grants from the Malaysian Ministry of Higher Education, FRGS/2/2010/ST/MUSM/03/2, FRGS/1/2014/ST03/MUSM/02/1 (to S.O.), FRGS/1/2016/STG03/MUSM/01/1 (to I.S.P) and Monash University Malaysia, SO-10-01 (to S.O.), IP-09-01 (to I.S.P).
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SO and ISP designed research; SO and ISP created antiserum for zebrafish Kiss2 receptor; MS and RA performed and analyzed the ISH and ICC experiments; MS performed Western blot analysis; MS and SO analyzed the data; and SO, MS, and ISP wrote the paper.
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All experimental procedures were performed under the guidelines of the Animal Ethics Committee of Monash University (approval number: MARP/2012/120).
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Supplementary Figure 1.
Photomicrographs of immunoreactivity of the mouse anti-human POMC antibody (POMC-Ab, A) and DIG-in situ hybridization of pomc mRNA (B) in the pituitary of zebrafish. In the RPD region, very weak POMC-immunoreactivity were observed (arrows). Scale bars: 100 μm (PNG 1606 kb)
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Ogawa, S., Sivalingam, M., Anthonysamy, R. et al. Distribution of Kiss2 receptor in the brain and its localization in neuroendocrine cells in the zebrafish. Cell Tissue Res 379, 349–372 (2020). https://doi.org/10.1007/s00441-019-03089-5
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DOI: https://doi.org/10.1007/s00441-019-03089-5