Wang T , Cao Z , Shen Z , Yang J , Chen X , Yang Z , Xu K , Xiang X , Yu Q , Song Y , Wang W , Tian Y , Sun L , Zhang L , Guo S , Zhou N .

41876154 National Science Foundation of China, 41406137 National Science Foundation of China, 41606150 National Science Foundation of China, COMS2019Q15 Center for Ocean Mega-Research of Science, Chinese Acadamy of Science

	Figure 1—figure supplement 1. Gene structure of the Apostichopus japonicus kisspeptin precursor.The signal peptide, predicted by the online SignalP-5.0 Server, is labeled in the box; the cleavage sites, predicted on the basis of previously known consensus cleavage motifs using the NeuroPred program, are highlighted in red; the glycine residues responsible for C-terminal amidation are highlighted in green; the cysteines paired in a disulfide-bonding structure are highlighted in light blue; and the predicted mature peptides with C-terminal amidation are underlined in black. The initiation codon (ATG) and the termination codon (TGA) are shown in bold.
	Figure 1. Gene structure, homology, and phylogenetic characterization of Apostichopus japonicus kisspeptin precursor (AjpreKiss).(A) Deduced amino-acid sequence of AjpreKiss. The signal peptide is labeled in the box with full lines; the cleavage sites are highlighted in red; glycine residues responsible for C-terminal amidation are highlighted in green; cysteines paired in a disulfide-bonding structure are highlighted in light blue; the predicted mature peptides, AjKiss1a and AjKiss1b, are noted by the blue and green underlines. (B) The organization of the AjpreKiss gene is compared with the zebrafish and human preKiss genes. The exon-intron data were obtained from the respective genomic sequences from NCBI (MRZV01001091.1, NC_007122.7, NC_007115.7 and NC_000001.11). DNA structure is shown with exons numbered in green bands. ATG represents the start methionine codon and TGA represents the stop codon. (C) Alignment of the predicted echinoderm kisspeptin core sequences and functionally characterized chordate kisspeptins. Sequences of Holothuria scabra, Holothuria glaberrima, Strongylocentrotus purpuratus, and Asterias rubens kisspeptins were predicted by Elphick’s lab (Semmens and Elphick, 2017; Suwansa-Ard et al., 2018). Vertebrate kisspeptin core sequences were obtained from GenBank with detailed sequences listed in Figure 1—source data 1. The color align property was generated using Sequence Manipulation Suite online. The percentage of sequences that must agree for identity or similarity coloring was set as 40%. (D) Phylogenetic tree of the kisspeptin precursor and four different neuropeptide outgroups (Mirabeau and Joly, 2013). The tree was constructed on the basis of approximately Maximum-Likelihood algorithms using FastTree two with pre-trimmed sequences. Local support values (%) were provided using the Shimodaira-Hasegawa (SH) test and are indicated by numbers at the nodes. The detailed complete sequences are listed in Figure 1—source data 2 and trimmed sequences are listed in Figure 1—source data 3.Figure 1—source data 1. Core sequences of kisspeptin from multiple species for alignment.Figure 1—source data 2. Amino-acid sequences of the kisspeptin precursor and outgroups for phylogenetic analysis.Figure 1—source data 3. Trimmed sequence alignment for phylogenetic tree construction.
	Figure 2—figure supplement 1. Sequence, topology and annotations of Apostichopus japonicus kisspeptin receptors (A: AjKissR1, B: AjKissR2) visualized using the Protter webservice.http://wlab.ethz.ch/protter/start/.
	Figure 2—figure supplement 2. Alignment of the deduced Apostichopus japonicus kisspeptin receptor amino-acid sequences with functionally characterized chordate GPR54 molecules from other species.Sequences of Branchiostoma japonicum kisspeptin receptor (BjKissR), Danio rerio kisspeptin receptors (DrKiss1Ra NP_001099149.2 and DrKiss1Rb NP_001104001.1), Xenopus tropicalis kisspeptin receptors (XtKiss1R NP_001163985.1, XtKissRa NP_001165296.1 and XtKissRb NP_001165295.1), Mus musculus kisspeptin receptor (MmKiss1R NP_444474.1), and Homo sapiens kisspeptin receptor (HsKiss1R NP_115940.2) were obtained from GenBank. Alignment was conducted using CLUSTAL W and the color align property was generated using Sequence Manipulation Suite online. The percentage of sequences that must agree for identity or similarity coloring was set as 60%.
	Figure 2—figure supplement 3. Transmembrane region sequence similarity of Apostichopus japonicus kisspeptin receptors to vertebrate kisspeptin receptors.Figure 2—figure supplement 3—source data 1 lists the detailed identities.Figure 2—figure supplement 3—source data 1. Primary metadata of detailed identities for Figure 2—figure supplement 3.
	Figure 2. Gene structure and phylogenetic characterization of Apostichopus japonicus kisspeptin receptors (AjKissR1 and AjKissR2).(A) DNA structures of AjKissR1 and AjKissR2. AjKissR1/2 DNA structure is shown with exons numbered in green bands. ATG represents the start methionine codon and TGA/TAG represents the stop codon. (B) Organization of the predicted protein structures. The seven transmembrane domains (TM1–TM7) are marked with red boxes. The N-terminal region and three extracellular (EC) rings are noted with blue boxes, and the C-terminal part and three intracellular (IC) rings are indicated with black boxes. Stop codons are represented by an asterisk. Arabic numbers under the bands indicate the nucleotide or amino acid sites. (C) Phylogenetic tree for kisspeptin, allatostatin-A and galanin receptors (KissR, AllaR and GalaR). The tree was constructed on the basis of approximately Maximum-Likelihood algorithms by FastTree two using AllaRs and GalaRs as outgroups (Ukena et al., 2014). Local support values were provided using the Shimodaira-Hasegawa (SH) test. The detailed sequences are listed in Figure 2—source data 1.Figure 2—source data 1. Amino-acid sequences of kisspeptin receptors and outgroups for phylogenetic analysis.
	Figure 3. Functional characteristics of Apostichopus japonicus kisspeptins and receptors.(A) The cells transiently expressing AjKissR1-EGFP or AjKissR2-EGFP were stained with cell membrane probe (DiI) and cell nucleus probe (DAPI) and detected by confocal microscopy. (B) After loading with Fura-2/AM, HEK293 cells expressing either FLAG-AjKissR1 or FLAG-AjKissR2 were exposed to the indicated concentrations of AjKiss1a (B1) and AjKiss1b (B2), and continuous fluorescence was recorded. AUC, Area Under the Curve. Figure 3B—source data 1 shows the primary metadata. (C) Internalization of AjKissR1-EGFP or AjKissR2-EGFP initiated by 1.0 μM of the indicated ligand was determined after a 60 min incubation by confocal microscopy. All pictures and data are representative of at least three independent experiments.Figure 3—source data 1. Primary metadata of Ca2+ mobilization assay for Figure 3B.
	Figure 4. Functional cross-activity between the A. japonicus and vertebrate Kisspeptin/Kisspeptin receptor systems.Intracellular Ca2+ mobilization in AjKissR1- (A) or AjKissR2-expressing (B) HEK293 cells was measured in response to 1.0 μM DrKiss1-10, DrKiss2-10, XtKiss1b-10, or HsKiss1-10 using Fura-2/AM. No Ca2+-mobilization-mediated activity was detected in AjKissR1- (C) or AjKissR2-expressing (D) HEK293 cells upon administration of the indicated concentrations of human neuropeptide S (HsNPS). Intracellular Ca2+ mobilization in human kisspeptin receptor (HsKiss1R)-expressing HEK293 cells was measured in response to 1.0 μM HsKiss1-10, AjKiss1a or AjKiss1b (E), as well as in zebrafish kisspeptin receptor (DrKiss1Ra or DrKiss1Rb)-expressing cells responding to 1.0 μM DrKiss1-10, AjKiss1a, or AjKiss1b (F, G). Figure 4—source data 1 shows the primary metadata. All data shown are representative of at least three independent experiments.Figure 4—source data 1. Primary metadata of Ca2+ mobilization assay for Figure 4A-G.
	Figure 5—figure supplement 1. Functional activity of FITC-AjKiss1a evaluated by intracellular Ca2+ mobilization detection.Intracellular Ca2+ mobilization in AjKissR1/2-expressing HEK293 cells was measured in response to 1.0 μM stimuli using Fura-2/AM.
	Figure 5. Apostichopus japonicus kisspeptin receptors are directly activated by kisspeptins via a Gαq-dependent pathway.(A) Intracellular Ca2+ mobilization in AjKissR1- and AjKissR2-expressing HEK293 cells was measured in response to 100 nM AjKiss1a or AjKiss1b, using cells that had been pre-treated for 12 hr with Gαi protein inhibitor (PTX, 100 ng/mL), or for 1 hr with DMSO, Gαq protein inhibitor (FR900359, 1.0 μM), PLC inhibitor (U73122, 10 μM), intracellular calcium chelator (BAPTA-AM, 100.0 μM), or extracellular calcium chelator (EGTA, 5.0 mM). Figure 5—source data 1 presents the primary metadata. Pictures shown are representative of at least three independent experiments. (B) Competitive binding of 1.0 μM fluorescein isothiocyanate (FITC)-AjKiss1a to AjKissR1 or AjKissR2 in the presence of the indicated concentration of AjKiss1a or AjKiss1b. Error bars represent the SEM for at least three independent experiments.Figure 5—source data 1. Primary metadata of Ca2+ mobilization assay and binding assay for Figure 5A and B.
	Figure 6—figure supplement 1. Functional activity of AjKiss1b-10.(A) Intracellular Ca2+ mobilization in AjKissR1/2-expressing HEK293 cells was measured in response to AjKiss1b-10 at the indicated concentrations using Fura-2/AM. (B) Internalization of overexpressed AjKissR1/2 initiated by 1.0 μM AjKiss1b-10 in AjKissR1–EGFP- or AjKissR2–EGFP-expressing HEK293 cells was determined by confocal microscopy. All data shown are representative of at least three independent experiments.
	Figure 6. ERK1/2 activation mediated by AjKissR1 or AjKissR2.(A) Concentration- and time-dependent effects of AjKiss1b-10 on ERK1/2 phosphorylation in HEK293 cells that were stably expressing FLAG–AjKissR1 or FLAG–AjKissR2. Cells were challenged with different concentrations of AjKiss1b-10 for 5 min or incubated with 1.0 μM AjKiss1b-10 for the indicated times. Immunoblots were quantified using a Bio-Rad Quantity One Imaging system. (B, C) ERK1/2 phosphorylation, activated by AjKiss1b-10, was blocked by PLC or PKC inhibitors. Serum-starved HEK293 cells expressing FLAG–AjKissR1 or FLAG–AjKissR2 were pre-treated with DMSO, PLC inhibitor (U73122, 10 μM), or PKC inhibitor (Gö6983, 10 μM) for 1 hr prior to AjKiss1b-10 stimulation (1.0 μM). (D, E) Role of various PKC isoforms in the activated signaling pathways of the sea cucumber kisspeptin receptor. HEK293 cells, co-transfected with FLAG–AjKissR1 or FLAG–AjKissR2 and different PKC-EGFP isoforms, were stimulated by 1.0 μM AjKiss1b-10 for the indicated times and then examined by confocal microscopy. Red arrows denote the recruitment of PKC–EGFP isoforms on the cell membrane. (F) Schematic diagram of agonist-induced A. japonicus kisspeptin receptor activation. AjKiss1b-10 binding to AjKissR1 or AjKissR2 activates the Gαq family of heterotrimeric G proteins, which leads to dissociation of the G protein subunits Gβγ, and activates PLC, leading to intracellular Ca2+ mobilization. This, in turn, activates PKC (isoform α and β) and stimulates the phosphorylation of ERK1/2. The ratio of p-ERK1/2 to total ERK1/2 was normalized to the peak value detected in the corresponding experiments (for example, the peak value of the ratio of AjKissR1/AjKiss1b-10 (10 μM) for the dose-dependent analysis, or of AjKissR1/AjKiss1b-10 (1.0 Aj) at 5 min for the time-course analysis). All pictures and data are representative of at least three independent experiments.
	Figure 7—figure supplement 1. Antibody specificities of anti-AjKiss1b-10 and anti-AjKissR1 IgG antibodies.(A) Western Blot analysis showing the specificity of the anti-AjKiss1b-10 IgG polyclonal antibody. AjKiss1b-10 and AjKiss1b (20 μL, 100 nM) were used as positive controls. (B) Antibody specificities of the anti-AjKissR1 IgG polyclonal antibody. AjKissR1–EGFP transfected or non-transfected cells were also tested. (C) Confocal microscopy analysis of the specificity of the anti-AjKissR1 IgG polyclonal antibody. AjKissR2–EGFP expressing cells were stained and scoped as a negative control. Cy3-conjugated goat anti-rabbit IgG was used as a secondary antibody. All data shown are representative of at least three independent experiments.
	Figure 7—figure supplement 2. General morphology and histology of Apostichopus japonicus tissues.(A–D) Light micrographs of H and E stained sections of respiratory tree, ovary, testis and muscle. CE, coelomic epithelium; BB, brown body; CM, cell membrane; NC, nucleus of oocytes; NU, nucleolus of oocytes; SE, spermatogenic epithelium; EM, epithelium of muscle; and MC, myocyte. (E) Gross anatomy of the anterior part (ANP). (F) Light micrographs of H and E stained sections of ANP and histology of nerve ring (NR). OS, outer surface; IR, internal region; CR, calcareous ring; AX, axon of neuron; and CB, cell body of neuron. All data shown are representative of at least three independent experiments.
	Figure 7—figure supplement 3. Inhibitory effect of pep234 on AjKissR1 and AjKissR2 activation.(A) Intracellular Ca2+ mobilization in AjKissR1- and AjKissR2-expressing HEK293 cells was measured in response to 100 nM AjKiss1a or AjKiss1b-10 pre-treated with DMSO or the KISS1 antagonist pep234 (1.0 μM). (B) ERK1/2 phosphorylation activity of kisspeptins and the inhibitory effect of pep234 in AjKissR1- and AjKissR2-expressing HEK293 cells. Samples were measured after 2 hr of ligand administration with or without pep234 pre-treatment. Error bars represent SEM for three independent experiments. Immunoblots were quantified using a Bio-Rad Quantity One Imaging system. All data shown are representative of at least three independent experiments.
	Figure 7—figure supplement 4. Functional activity of AjKiss1b-10 in Apostichopus japonicus.(A) Expressional change of the gene encoding the glycolytic enzyme pyruvate kinase (PK) in tissues of sea cucumbers responds to a 40-day administration of AjKiss1b-10. RET, respiratory tree; MUS, muscle; INT, intestine; and ANP, anterior part of sea cucumber. (B) E2 concentration in the coelomic fluid of sea cucumbers did not significantly respond to AjKiss1b-10. Each error bar represents SEM (n = 5 biological replicates). * indicates significant difference (PBS vs. AjKiss1b-10, p=0.0188), and ** indicates extremely significant difference (PBS vs. AjKiss1b-10, p=0.0002), as determined by ANOVA followed by Tukey’s multiple comparisons test. Figure 7—figure supplement 4—source data 1 lists the detailed primary metadata and statistics.Figure 7—figure supplement 4—source data 1. Primary metadata of qPCR assay and E2 concentration for Figure 7—figure supplement 4A and B.
	Figure 7—figure supplement 5. Mean body weight (A) and tissue index (B) change over annual investigation.Relative gut mass (RGM) and relative ovary weight (ROW) indicate the ratio of tissue weight/body weight. The number of animals used for all samples is six, except for the number of ovary samples, with one in NOV (November), three in DEC (December), FEB (February) and JUN (June), five in MAR (March), and six in APR (April) and MAY (May). Figure 7—figure supplement 5—source data 1 lists the primary metadata.Figure 7—figure supplement 5—source data 1. Primary metadata of body weight and tissue index in annual investigation for Figure 7—figure supplement 5A and B.
	Figure 7. Physiological function analysis of kisspeptin signaling systems in Apostichopus japonicus.(A) Western Blot analysis of A. japonicus kisspeptin precursor and kisspeptin receptor (AjKissR1) in different tissues of sea cucumber. INT, intestine; RET, respiratory tree; ANP, anterior part; OVA, ovary; TES, testis; MUS, muscle; and BOW, body wall. (B) Immunofluorescence histochemical staining of A. japonicus kisspeptin precursor and AjKissR1 in RET, OVA, TES, MUS (B1) and nerve ring (B2) of the sea cucumber. CE, coelomic epithelium; BB, brown body; CM, cell membrane; SE, spermatogenic epithelium; EM, epithelium of muscle; OS, outer surface; and IR, internal region. (C) ERK1/2 phosphorylation activity of kisspeptins and the inhibitory effect of a vertebrate kisspeptin antagonist (pep234) on the cultured ovary of sea cucumber. Samples were collected and fixed after 2 hr of ligand administration with or without a 4-hr pre-treatment with pep234, in optimized L15 medium at 18°C. Error bars represent SEM for three independent experiments. Immunoblots were quantified using a Bio-Rad Quantity One Imaging system. (D) Immunofluorescence histochemical staining of p-ERK signal in cultured oocytes of sea cucumber. Samples were collected and fixed after 2 hr of ligand administration with or without a 4-hr pretreatment with pep234, in optimized L15 medium at 18°C. NC indicates the nucleus of oocytes. (E, F) Variation of body weight and tissue index (ratio of tissue weight/body weight) over 40 days of stimulus treatment. Each symbol and vertical bar represent mean ± SEM (n = 5 animals). ** indicates extremely significant differences (p=0.0001), as demonstrated by one-way ANOVA followed by Tukey’s multiple comparisons test. (G) Degenerated intestine in AjKiss1b-10 treated sea cucumbers. (H) Heatmap showing the expression profile of A. japonicus kisspeptin and kisspeptin receptors (AjKissR1/R2 and AjKiss1) in different tissues and developmental stages of sea cucumber. The variation in color represents the relative expression level of each gene in different samples (normalized against the peak values in all samples and logarithmized). The number of animals used for all samples is six, except for the number of ovary samples, with one in NOV (November) and JUN (June), three in DEC (December) and FEB (February), five in MAR (March), and six in APR (April) and MAY (May), and in testis, with two in NOV (November) and DEC (December), four in FEB (February) and MAR (March), and six in APR (April) and MAY (May). Figure 7—source data 1 represents the primary metadata. All pictures and data are representative of at least three independent experiments.Figure 7—source data 1. Primary metadata of body weight, tissue index and qPCR assay for Figure 7E, F and H.
	Figure 8. Recently identified Kisspeptin or Kisspeptin receptor genes among some deuterostomes.The species, indicated by silhouette images downloaded from the PhyloPic database, were clustered in a phylogenetic tree and classified by different colors. Red highlighted ‘R’ indicates a whole-genome duplication event. Kiss/KissR indicates the identified Kisspeptin/Kisspeptin receptor gene, and KissL/KissRL indicates a predicted Kisspeptin-like/Kisspeptin-like receptor gene. Dashed symbols indicate pseudogenes. Arabic numerals indicate the number of genes identified or predicted from public data. The evolutionary tree of the indicated species was modified from Pasquier et al., 2014. Image credits: all silhouettes from PhyloPic, human by T Michael Keeseyacorn; mouse by Anthony Caravaggi; platypus by Sarah Werning; duck by Sharon Wegner-Larsen; crocodile by B Kimmel; turtle by Roberto Díaz Sibaja; python by V Deepak; frog uncredited; coelacanth by Yan Wong; zebrafish by Jake Warner; spotted gar by Milton Tan; Branchiostoma by Mali'o Kodis, photograph by Hans Hillewaert; acorn worm by Mali'o Kodis, drawing by Manvir Singh; starfish by Hans Hillewaert and T Michael Keesey; sea cucumber by Lauren Sumner-Rooney; sea urchin by Jake Warner.

Albers-Wolthers, Identification of a novel kisspeptin with high gonadotrophin stimulatory activity in the dog. 2014, Pubmed

Albers-Wolthers, Identification of a novel kisspeptin with high gonadotrophin stimulatory activity in the dog. 2014, Pubmed
Arendt, From nerve net to nerve ring, nerve cord and brain--evolution of the nervous system. 2016, Pubmed
Bakos, The Role of Hypothalamic Neuropeptides in Neurogenesis and Neuritogenesis. 2016, Pubmed
Biran, Molecular identification and functional characterization of the kisspeptin/kisspeptin receptor system in lower vertebrates. 2008, Pubmed
Burbridge, Development of the Neuroendocrine Hypothalamus. 2016, Pubmed
Capella-Gutiérrez, trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. 2009, Pubmed
Castaño, Intracellular signaling pathways activated by kisspeptins through GPR54: do multiple signals underlie function diversity? 2009, Pubmed
Chen, Neuropeptide precursors and neuropeptides in the sea cucumber Apostichopus japonicus: a genomic, transcriptomic and proteomic analysis. 2019, Pubmed , Echinobase
Ciaramella, Kisspeptin and Cancer: Molecular Interaction, Biological Functions, and Future Perspectives. 2018, Pubmed
Comninos, Kisspeptin modulates sexual and emotional brain processing in humans. 2017, Pubmed
Dhillo, Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. 2005, Pubmed
Dhillo, Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women. 2007, Pubmed
Elphick, From gonadotropin-inhibitory hormone to SIFamides: are echinoderm SALMFamides the "missing link" in a bilaterian family of neuropeptides that regulate reproductive processes? 2013, Pubmed , Echinobase
Elphick, The Evolution and Variety of RFamide-Type Neuropeptides: Insights from Deuterostomian Invertebrates. 2014, Pubmed , Echinobase
Franssen, The kisspeptin receptor: A key G-protein-coupled receptor in the control of the reproductive axis. 2018, Pubmed
Gottsch, A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. 2004, Pubmed
Hall, The crown-of-thorns starfish genome as a guide for biocontrol of this coral reef pest. 2017, Pubmed , Echinobase
Hartenstein, The neuroendocrine system of invertebrates: a developmental and evolutionary perspective. 2006, Pubmed
Higo, Mapping of Kisspeptin Receptor mRNA in the Whole Rat Brain and its Co-Localisation with Oxytocin in the Paraventricular Nucleus. 2016, Pubmed
Huang, Kisspeptin/GPR54 signaling restricts antiviral innate immune response through regulating calcineurin phosphatase activity. 2018, Pubmed
Javed, The role of kisspeptin signalling in the hypothalamic-pituitary-gonadal axis--current perspective. 2015, Pubmed
Jiang, In vivo and vitro characterization of the effects of kisspeptin-13, endogenous ligands for GPR54, on mouse gastrointestinal motility. 2017, Pubmed
Jékely, Global view of the evolution and diversity of metazoan neuropeptide signaling. 2013, Pubmed
Katugampola, Kisspeptin Is a Novel Regulator of Human Fetal Adrenocortical Development and Function: A Finding With Important Implications for the Human Fetoplacental Unit. 2017, Pubmed
Kirby, International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin receptor nomenclature, distribution, and function. 2010, Pubmed
Kotani, The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. 2001, Pubmed
Lapadula, Effects of Oncogenic Gαq and Gα11 Inhibition by FR900359 in Uveal Melanoma. 2019, Pubmed
Lee, Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. 2009, Pubmed
Li, Internalization of the human nicotinic acid receptor GPR109A is regulated by G(i), GRK2, and arrestin3. 2010, Pubmed
Livak, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. 2001, Pubmed
Lü, Cloning, Characterization, and Expression Profile of Estrogen Receptor in Common Chinese Cuttlefish, Sepiella japonica. 2016, Pubmed
Mirabeau, Molecular evolution of peptidergic signaling systems in bilaterians. 2013, Pubmed
Moore, Regulation of receptor trafficking by GRKs and arrestins. 2007, Pubmed
Muir, AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. 2001, Pubmed
Nakajo, Evolutionally Conserved Function of Kisspeptin Neuronal System Is Nonreproductive Regulation as Revealed by Nonmammalian Study. 2018, Pubmed
Oakley, Kisspeptin signaling in the brain. 2009, Pubmed
Odekunle, Ancient role of vasopressin/oxytocin-type neuropeptides as regulators of feeding revealed in an echinoderm. 2019, Pubmed , Echinobase
Ohga, Identification, characterization, and expression profiles of two subtypes of kisspeptin receptors in a scombroid fish (chub mackerel). 2013, Pubmed
Ohtaki, Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. 2001, Pubmed
Pasquier, Molecular evolution of GPCRs: Kisspeptin/kisspeptin receptors. 2014, Pubmed
Popa, The role of kisspeptins and GPR54 in the neuroendocrine regulation of reproduction. 2008, Pubmed
Price, FastTree 2--approximately maximum-likelihood trees for large alignments. 2010, Pubmed
Roseweir, The role of kisspeptin in the control of gonadotrophin secretion. 2009, Pubmed
Semmens, Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution. 2016, Pubmed , Echinobase
Semmens, The evolution of neuropeptide signalling: insights from echinoderms. 2017, Pubmed , Echinobase
Seymour, Development of an excitatory kisspeptin projection to the oxytocin system in late pregnancy. 2017, Pubmed
Shen, BNGR-A25L and -A27 are two functional G protein-coupled receptors for CAPA periviscerokinin neuropeptides in the silkworm Bombyx mori. 2017, Pubmed
Shenoy, Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination. 2003, Pubmed
Simakov, Hemichordate genomes and deuterostome origins. 2015, Pubmed , Echinobase
Smith, The neuropeptidome of the Crown-of-Thorns Starfish, Acanthaster planci. 2017, Pubmed , Echinobase
Song, Glucagon regulates hepatic kisspeptin to impair insulin secretion. 2014, Pubmed
Subramanian, Evolview v3: a webserver for visualization, annotation, and management of phylogenetic trees. 2019, Pubmed
Suwansa-Ard, Transcriptomic discovery and comparative analysis of neuropeptide precursors in sea cucumbers (Holothuroidea). 2018, Pubmed , Echinobase
Tang, The kiss/kissr systems are dispensable for zebrafish reproduction: evidence from gene knockout studies. 2015, Pubmed
Tessmar-Raible, The evolution of neurosecretory centers in bilaterian forebrains: insights from protostomes. 2007, Pubmed
Tessmar-Raible, Conserved sensory-neurosecretory cell types in annelid and fish forebrain: insights into hypothalamus evolution. 2007, Pubmed
Uenoyama, The roles of kisspeptin revisited: inside and outside the hypothalamus. 2016, Pubmed
Ukena, Molecular evolution of GPCRs: 26Rfa/GPR103. 2014, Pubmed
Vandesompele, Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. 2002, Pubmed
Wang, Demonstration of a Functional Kisspeptin/Kisspeptin Receptor System in Amphioxus With Implications for Origin of Neuroendocrine Regulation. 2017, Pubmed
Wang, Apoptosis Induction and Detection in a Primary Culture of Sea Cucumber Intestinal Cells. 2020, Pubmed , Echinobase
Zandawala, Discovery of novel representatives of bilaterian neuropeptide families and reconstruction of neuropeptide precursor evolution in ophiuroid echinoderms. 2017, Pubmed , Echinobase
Zhang, The sea cucumber genome provides insights into morphological evolution and visceral regeneration. 2017, Pubmed , Echinobase
Zhu, Gene structure, expression, and DNA methylation characteristics of sea cucumber cyclin B gene during aestivation. 2016, Pubmed , Echinobase
Zmora, Differential and gonad stage-dependent roles of kisspeptin1 and kisspeptin2 in reproduction in the modern teleosts, morone species. 2012, Pubmed