New observations on the development of the gonadotropin-releasing hormone system in the mouse

Wu, Tao; Gibson, M.E.; Rogers, Marie-Christine; Silverman, Ann‐Judith

doi:10.1002/(sici)1097-4695(199712)33:7<983::aid-neu9>3.0.co;2-4

Cited by 55 publications

(43 citation statements)

References 80 publications

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“…Using a simple explant culture that supports the specification of GnRH neuronal fate, we observed robust increases in the number of GnRH neurons over 3 d in explants isolated from E10.5 and E11.0, but not E10.0 and E11.5, embryos. These two time points (E10.5 and E11.0) coincided with the period during which the majority of GnRH neurons emerged in vivo (1,21,36). Interestingly, this increase in our culture system was not due to neurogenesis per se because explants treated with BrDU for the first 24 h failed to incorporate this mitotic marker.…”

Section: Discussionmentioning

confidence: 62%

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Developmental Regulation of Gonadotropin-Releasing Hormone Neurons by Fibroblast Growth Factor Signaling

Gill¹,

Moenter²,

Tsai³

2004

Endocrinology

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GnRH neurons are central to the initiation and maintenance of reproductive function in diverse vertebrates. The formation of a functional GnRH system during development is a highly complex event that likely requires extensive guidance by neurotrophic factors. In this study, we examined whether members of the fibroblast growth factor (FGF) family are critically involved in the development of endogenous GnRH neurons. Immunocytochemistry revealed the presence of FGF receptors (FGFRs) 1, 2, and 3, but not 4, in embryonic day (E) 10.5 medial nasal placode, an area and time consistent with the first appearance of GnRH neurons in mice. Dual immunocytochemistry confirmed the presence of FGFRs 1 and 3, but not 2 and 4, in a substantial fraction of E15.5 and postnatal day (P) 3 GnRH neurons. To examine whether FGF signaling was essential for the specification of GnRH neuronal fate, a nasal explant culture that supported the in vitro emergence of GnRH neurons from E10.5 noses was established. In this system, the addition of SU5402, a FGFR antagonist, suppressed the emergence of GnRH neurons. Lastly, we investigated whether FGF signaling altered the extension of neurites in cultures of dispersed GnRH neurons. The addition of FGF2 to E15.5 and P3 GnRH neurons expressing the green fluorescent protein significantly stimulated neurite outgrowth (E15.5 and P3) and branching (P3), suggesting a regulatory role of FGFs in GnRH axon targeting. Together these results demonstrated that FGF signaling critically regulates multiple phases of development in a neuroendocrine system essential for vertebrate reproduction.

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Section: Discussionmentioning

confidence: 62%

“…GnRH neurons were first detected in the mouse at E10.5 by the expression of GnRH mRNA and the production of the GnRH peptide (1,21,36). Currently there is no reliable way to identify GnRH precursors before the production of GnRH mRNA or peptide (4).…”

Section: Discussionmentioning

confidence: 99%

Developmental Regulation of Gonadotropin-Releasing Hormone Neurons by Fibroblast Growth Factor Signaling

Gill¹,

Moenter²,

Tsai³

2004

Endocrinology

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“…The ontogeny of ARH projections contrasts with that of afferents to the paraventricular nucleus from the brainstem, which are present at birth (Rinaman, 2001). Similarly, the neurohypophyseal pathway from the PVH, and projections from GnRH neurons, to the median eminence appear to be primarily formed by birth (Daikoku et al, 1984;Wu et al, 1997). Magnocellular neurons also appear to establish their projections to the posterior pituitary before birth.…”

Section: Discussionmentioning

confidence: 95%

Formation of Projection Pathways from the Arcuate Nucleus of the Hypothalamus to Hypothalamic Regions Implicated in the Neural Control of Feeding Behavior in Mice

Bouret¹,

Draper²,

Simerly³

2004

J. Neurosci.

513

458

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The arcuate nucleus of the hypothalamus (ARH) is a critical component of forebrain pathways that regulate a variety of neuroendocrine functions, including an important role in relaying leptin signals to other parts of the hypothalamus. However, neonatal rodents do not lose weight in response to leptin treatment in the same way as do adults, suggesting that certain aspects of leptin signaling pathways in the hypothalamus may not be mature. We tested this possibility by using DiI axonal labeling to examine the development of projections from the ARH to other parts of the hypothalamus in neonatal mice, paying particular attention to the innervation of the paraventricular nucleus (PVH), the dorsomedial nucleus (DMH), and the lateral hypothalamic area (LHA), each of which have been implicated in the regulation of feeding. The results indicate that ARH projections are quite immature at birth and appear to innervate the DMH, PVH, and LHA in succession, within distinct temporal domains. The projections from the ARH to the DMH develop rapidly and are established by the sixth postnatal day (P6), whereas those to the PVH develop significantly later, with the mature pattern of innervation first apparent between postnatal day 8 (P8)-P10. Furthermore, the ability of leptin to activate Fos in the PVH, DMH, and LHA appears to be agedependent and correlates with the arrival of ARH projections to each nucleus. Taken together, these findings provide new insight into development of hypothalamic circuits and suggest an anatomical basis for the delayed postnatal regulation of food intake and body weight by leptin.

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“…S1). In the mouse brain there are only ∼800 GnRH neurons, which are widely dispersed across the medial hypothalamus and basal forebrain (20). To facilitate identification of GnRH neurons we labeled brain slices from adult male and female transgenic mice expressing GFP under the control of the GnRH promoter (GnRH::GFP) (21).…”

Section: Resultsmentioning

confidence: 99%

Primary cilia enhance kisspeptin receptor signaling on gonadotropin-releasing hormone neurons

Koemeter-Cox

Sherwood

Green

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Most central neurons in the mammalian brain possess an appendage called a primary cilium that projects from the soma into the extracellular space. The importance of these organelles is highlighted by the fact that primary cilia dysfunction is associated with numerous neuropathologies, including hyperphagia-induced obesity, hypogonadism, and learning and memory deficits. Neuronal cilia are enriched for signaling molecules, including certain G protein-coupled receptors (GPCRs), suggesting that neuronal cilia sense and respond to neuromodulators in the extracellular space. However, the impact of cilia on signaling to central neurons has never been demonstrated. Here, we show that the kisspeptin receptor (Kiss1r), a GPCR that is activated by kisspeptin to regulate the onset of puberty and adult reproductive function, is enriched in cilia projecting from mouse gonadotropin-releasing hormone (GnRH) neurons. Interestingly, GnRH neurons in adult animals are multiciliated and the percentage of GnRH neurons possessing multiple Kiss1r-positive cilia increases during postnatal development in a progression that correlates with sexual maturation. Remarkably, disruption of cilia selectively on GnRH neurons leads to a significant reduction in kisspeptin-mediated GnRH neuronal activity. To our knowledge, this result is the first demonstration of cilia disruption affecting central neuronal activity and highlights the importance of cilia for proper GPCR signaling.GPR54 | neuronal primary cilia | electrophysiology

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New observations on the development of the gonadotropin-releasing hormone system in the mouse

Cited by 55 publications

References 80 publications

Developmental Regulation of Gonadotropin-Releasing Hormone Neurons by Fibroblast Growth Factor Signaling

Developmental Regulation of Gonadotropin-Releasing Hormone Neurons by Fibroblast Growth Factor Signaling

Formation of Projection Pathways from the Arcuate Nucleus of the Hypothalamus to Hypothalamic Regions Implicated in the Neural Control of Feeding Behavior in Mice

Primary cilia enhance kisspeptin receptor signaling on gonadotropin-releasing hormone neurons

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