Expression and localization of FGF-1 in the developing rat olfactory system

Key, Brian; Treloar, Helen B.; Wangerek, L.; Ford, Miriam D.; Nurcombe, Victor

doi:10.1002/(sici)1096-9861(19960304)366:2<197::aid-cne1>3.0.co;2-0

Cited by 37 publications

(20 citation statements)

References 46 publications

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“…These results are not surprising because patterning and morphogenesis of the nasal placode and the outgrowth of olfactory axons require FGF signaling (31). In further support of our data, in situ hybridization revealed that the neuroepithelium of the nasal placode expressed mRNAs for not only FGFRs 1 and 2 but also up to seven forms of FGFs (32)(33)(34)(35). Thus, the period during which GnRH neuronal fate is specified coincided with not only the presence of FGFRs but also the production of diverse FGF ligands required to activate FGFRs.…”

Section: Discussionsupporting

confidence: 85%

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: Discussionsupporting

confidence: 85%

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

Gill¹,

Moenter²,

Tsai³

2004

Endocrinology

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“…Moreover, a number of FGFs, including FGF2, are expressed in and around OE at various stages of development (DeHamer et al, 1994;Hsu et al, 2001;Kawauchi et al, 2004;Key et al, 1996). However, two observations argue that FGF2 is unlikely to be a crucial regulator of developmental neurogenesis in the OE.…”

Section: Introductionmentioning

confidence: 99%

Fgf8expression defines a morphogenetic center required for olfactory neurogenesis and nasal cavity development in the mouse

et al. 2005

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In vertebrate olfactory epithelium (OE), neurogenesis proceeds continuously, suggesting that endogenous signals support survival and proliferation of stem and progenitor cells. We used a genetic approach to test the hypothesis that Fgf8 plays such a role in developing OE. In young embryos, Fgf8 RNA is expressed in the rim of the invaginating nasal pit (NP), in a small domain of cells that overlaps partially with that of putative OE neural stem cells later in gestation. In mutant mice in which the Fgf8 gene is inactivated in anterior neural structures, FGF-mediated signaling is strongly downregulated in both OE proper and underlying mesenchyme by day 10 of gestation. Mutants survive gestation but die at birth,lacking OE, vomeronasal organ (VNO), nasal cavity, forebrain, lower jaw,eyelids and pinnae. Analysis of mutants indicates that although initial NP formation is grossly normal, cells in the Fgf8-expressing domain undergo high levels of apoptosis, resulting in cessation of nasal cavity invagination and loss of virtually all OE neuronal cell types. These findings demonstrate that Fgf8 is crucial for proper development of the OE,nasal cavity and VNO, as well as maintenance of OE neurogenesis during prenatal development. The data suggest a model in which Fgf8expression defines an anterior morphogenetic center, which is required not only for the sustenance and continued production of primary olfactory (OE and VNO) neural stem and progenitor cells, but also for proper morphogenesis of the entire nasal cavity.

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“…As noted above, it has been established that other cell types provide trophic support for basal cells and OSNs (49). Several studies have provided evidence that OSNs, basal cells, sustentacular cells, and OECs express molecular regulators of the proliferation and differentiation of OSN progenitors, including TGF-␤, FGFs, LIF, IGF-1, and OMP (20,21,25,30). Our study provides evidence that macrophages also contribute to the regulation of the survival of OSNs and to the proliferation, differentiation, and maturation of OSN progenitors through the expression of growth, survival, and proliferative factors.…”

Section: Discussionmentioning

confidence: 96%

Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium

Borders

Hersh

Getchell

et al. 2007

Physiological Genomics

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Resident and recruited olfactory epithelial macrophages participate in the regulation of the survival, degeneration, and replacement of olfactory sensory neurons (OSNs). We have reported that liposome-encapsulated clodronate (Lip-C) induced selective and statistically significant depletion of macrophages in the OE of sham and 48 h OBX mice (38 and 35%, respectively) that resulted in increased OSN apoptosis and decreased numbers of mature OSNs and proliferating basal cells compared to controls (Lip-O). The aim of this study was to identify molecular mechanisms by which the selective depletion of macrophages in the OE resulted in these cellular changes by using a microarray expression pattern analysis. A 2ϫ2 ANOVA identified 4,085 overall significantly (P Ͻ 0.01) regulated genes in the OE of Lip-O and Lip-C sham and 48 h OBX mice, and further statistical analysis using pairwise comparisons identified 4,024 genes that had either a significant (P Ͻ 0.01) treatment main effect (n ϭ 2,680), group main effect (n ϭ 778), or interaction effect (n ϭ 980). The mean hybridization signals of immune response genes, e.g., Cxcr4, and genes encoding growth factors and neurogenesis regulators, e.g., Hdgf and Neurod1, respectively, were primarily lower in Lip-C mice compared with Lip-O mice. Apoptosis genes, e.g., Bak1, were also differentially regulated in Lip-C and/or OBX mice. Expression patterns of selected genes were validated with real-time RT-PCR; immunohistochemistry was used to localize selected gene products. These results identified the differential regulation of several novel genes through which alternatively activated macrophages regulate OSN progenitor cell proliferation, differentiation, and maturation, and the survival of OSNs.clodronate; liposomes; microarray; immune response THE DYNAMIC ENVIRONMENT of the olfactory epithelium (OE), where olfactory sensory neurons (OSNs) undergo apoptosis and are replaced from a pool of basal progenitor cells throughout life (9,41,49), continues to provide insight into mechanisms of neuroprotection, neuronal apoptosis, and neurogenesis. More specifically, recent studies (6,23,33) on the interaction between the immune system and neurogenesis in the OE have strengthened the case for the participation of macrophages in the regulation of OSN survival and the proliferation, differentiation, and maturation of OSN basal progenitor cells in the unperturbed OE and during OE remodeling as a result of olfactory bulbectomy (OBX)-induced OSN apoptosis.

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Expression and localization of FGF-1 in the developing rat olfactory system

Cited by 37 publications

References 46 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

Fgf8expression defines a morphogenetic center required for olfactory neurogenesis and nasal cavity development in the mouse

Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium

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