東京大学 · 生化学・遺伝学・分子生物学
Professor Kataaki Okubo's research lab focuses on the molecular and cellular mechanisms underlying reproductive neuroendocrinology and sexual differentiation in teleost fish, particularly the medaka. The lab investigates the evolution and function of neuropeptides such as gonadotropin-releasing hormone (GnRH) and neuropeptide B (NPB), as well as the roles of steroid hormones and their receptors in shaping sexually dimorphic brain development and behavior. A central theme is understanding how hormonal signals, especially estrogen, regulate gene expression and neural circuits to control reproduction and mating behavior in a sex-specific and reversible manner. The lab employs comparative genomics, molecular biology, and neuroanatomical approaches to uncover conserved and teleost-specific mechanisms of brain plasticity and endocrine regulation.
Figures are computed from collected data and may differ slightly.
The neuropeptide gonadotropin-releasing hormone (GnRH) has a central role in the neural control of vertebrate reproduction. This review describes an overview of what is currently known about GnRH in vertebrates in the context of its structural and functional evolution. A large body of evidence has demonstrated the existence of three paralogous genes for GnRH (GnRH1, GnRH2 and GnRH3) in the vertebrate lineage. They are most probably the products of whole-genome duplications that occurred early in
Neurons that synthesize and release GnRH are essential for the central regulation of reproduction. Evidence suggests that forebrain GnRH neurons originate in the olfactory placode and migrate to their final destinations, although this is still a matter of controversy. X-linked Kallmann syndrome (X-KS), characterized by failed gonadal function secondary to deficient gonadotropin secretion, is caused by a mutation in KAL1, which is suggested to regulate the migration of forebrain GnRH neurons. Bec
We report the identification and characterization of two distinct GnRH receptor (GnRH-R) subtypes, designated GnRH-R1 and GnRH-R2, in a model teleost, the medaka Oryzias latipes. These seven-transmembrane receptors of the medaka contain a cytoplasmic C-terminal tail, which has been found in all other nonmammalian GnRH-Rs cloned to date. The GnRH-R1 gene is composed of three exons separated by two introns, whereas the GnRH-R2 gene has an additional intron and therefore consists of four exons and
The brain of teleost fish exhibits a significant degree of sexual plasticity, even in adulthood. This unique feature is almost certainly attributable to a teleost-specific sexual differentiation process of the brain, which remains largely unknown. To dissect the molecular basis of sexual differentiation of the teleost brain, we searched for genes differentially expressed between both sexes in the medaka brain. One gene identified in the screen, cyp19a1b, which encodes the steroidogenic enzyme ar
To dissect the molecular and cellular basis of sexual differentiation of the teleost brain, which maintains marked sexual plasticity throughout life, we examined sex differences in neural expression of all subtypes of nuclear oestrogen and androgen receptors (ER and AR) in medaka. All receptors were differentially expressed between the sexes in specific nuclei in the forebrain. The most pronounced sex differences were found in several nuclei in the ventral telencephalic and preoptic areas, where
Male and female animals display innate sex-specific mating behaviors. In teleost fish, altering the adult sex steroid milieu can effectively reverse sex-typical mating behaviors, suggesting remarkable sexual lability of their brains as adults. In the teleost medaka, neuropeptide B (NPB) is expressed female-specifically in the brain nuclei implicated in mating behavior. Here, we demonstrate that NPB is a direct mediator of estrogen action on female mating behavior, acting in a female-specific but
We isolated and characterized two distinct cDNAs for mammalian gonadotropin-releasing hormone (mGnRH) and chicken GnRH-II (cGnRH-II) precursors from the Japanese eel by rapid amplification of cDNA ends. Each GnRH precursors were composed of a signal peptide, a GnRH decapeptide, a processing site and a GnRH-associated peptide. Northern blot and reverse transcription-polymerase chain reaction analysis revealed that the mGnRH precursor gene is expressed in all tissues tested including the brain, pi
Aromatase, the key enzyme responsible for estrogen biosynthesis, is present in the brain of all vertebrates. Much evidence has accumulated that aromatase is highly and exclusively expressed in proliferating mature radial glial cells in the brain of teleost fish even in adulthood, unlike in other vertebrates. However, the physiological significance of this expression remains unknown. We recently found that aromatase is female-specifically expressed in the optic tectum of adult medaka fish. In the
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
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