scholarly journals Quantitative assessment of fibroblast growth factor receptor 1 expression in neurons and glia

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3173 ◽  
Author(s):  
Lisha Choubey ◽  
Jantzen C. Collette ◽  
Karen Müller Smith
Keyword(s):  
Glial Cells ◽  
Synapse Formation ◽  
Fluorescent Protein ◽  
Growth Factor Receptor ◽  
Neuropsychiatric Disorders ◽  
Cell Types ◽  
Lipid Binding ◽  
Bergmann Glia ◽  
Fibroblast Growth ◽  
Postnatal Maturation

BackgroundFibroblast growth factors (FGFs) and their receptors (FGFRs) have numerous functions in the developing and adult central nervous system (CNS). For example, the FGFR1 receptor is important for proliferation and fate specification of radial glial cells in the cortex and hippocampus, oligodendrocyte proliferation and regeneration, midline glia morphology and soma translocation, Bergmann glia morphology, and cerebellar morphogenesis. In addition, FGFR1 signaling in astrocytes is required for postnatal maturation of interneurons expressing parvalbumin (PV). FGFR1 is implicated in synapse formation in the hippocampus, and alterations in the expression ofFgfr1and its ligand,Fgf2accompany major depression. Understanding which cell types expressFgfr1during development may elucidate its roles in normal development of the brain as well as illuminate possible causes of certain neuropsychiatric disorders.MethodsHere, we used a BAC transgenic reporter line to traceFgfr1expression in the developing postnatal murine CNS. The specific transgenic line employed was created by the GENSAT project,tgFGFR1-EGFPGP338Gsat, and includes a gene encoding enhanced green fluorescent protein (EGFP) under the regulation of theFgfr1promoter, to traceFgfr1expression in the developing CNS. Unbiased stereological counts were performed for several cell types in the cortex and hippocampus.ResultsThis model reveals thatFgfr1is primarily expressed in glial cells, in both astrocytes and oligodendrocytes, along with some neurons. Dual labeling experiments indicate that the proportion of GFP+ (Fgfr1+) cells that are also GFAP+ increases from postnatal day 7 (P7) to 1 month, illuminating dynamic changes inFgfr1expression during postnatal development of the cortex. In postnatal neurogenic areas, GFP expression was also observed in SOX2, doublecortin (DCX), and brain lipid-binding protein (BLBP) expressing cells.Fgfr1is also highly expressed in DCX positive cells of the dentate gyrus (DG), but not in the rostral migratory stream.Fgfr1driven GFP was also observed in tanycytes and GFAP+ cells of the hypothalamus, as well as in Bergmann glia and astrocytes of the cerebellum.ConclusionsThetgFGFR1-EGFPGP338Gsatmouse model expresses GFP that is congruent with known functions of FGFR1, including hippocampal development, glial cell development, and stem cell proliferation. Understanding which cell types expressFgfr1may elucidate its role in neuropsychiatric disorders and brain development.

scholarly journals Quantitative assessment of Fgfr1 expression in neurons and glia

2016 ◽  
Author(s):  
Lisha Choubey ◽  
Jantzen C Collette ◽  
Karen Muller Smith
Keyword(s):  
Glial Cells ◽  
Synapse Formation ◽  
Fluorescent Protein ◽  
Neuropsychiatric Disorders ◽  
Cell Types ◽  
Lipid Binding ◽  
Bergmann Glia ◽  
Radial Glial Cells ◽  
Postnatal Maturation ◽  
Green Fluorescent

Fibroblast growth factors (FGFs) and their receptors (FGFRs) have numerous functions in the developing and adult CNS. For example, the FGFR1 receptor is important for proliferation of radial glial cells in the cortex and hippocampus, oligodendrocyte proliferation and regeneration, midline glia morphology and soma translocation, Bergmann glia morphology, and cerebellar morphogenesis. In addition, FGFR1 signaling in astrocytes is required for postnatal maturation of interneurons expressing parvalbumin (PV). FGFR1 is implicated in synapse formation in the hippocampus, and alterations in the expression of Fgfr1 and its ligand, Fgf2 accompany major depression. Understanding which cell types express Fgfr1 during development may elucidate its roles in normal development of the brain as well as illuminate possible causes of certain neuropsychiatric disorders. Here, we used a BAC transgenic reporter line to trace Fgfr1 expression in the developing murine CNS. The specific transgenic line employed was created by the GENSAT project, tgFGFR1-EGFPGP338Gsat, and includes a gene encoding enhanced green fluorescent protein (EGFP) under the regulation of the Fgfr1 promoter, to trace Fgfr1 expression in the developing CNS. This model reveals that Fgfr1 is primarily expressed in glial cells, in both astrocytes and oligodendrocytes, along with some neurons. Dual labeling experiments indicate that the proportion of GFP+ (Fgfr1+) cells that are also GFAP+ increases from postnatal day 7 (P7) to 1 month, illuminating dynamic changes in Fgfr1 expression during postnatal development of the cortex. In postnatal neurogenic areas, GFP expression was also observed in SOX2, doublecortin (DCX), and brain lipid-binding protein (BLBP) expressing cells. Fgfr1 is also highly expressed in DCX positive cells of the dentate gyrus, but not in the rostral migratory stream. Fgfr1 driven GFP was also observed in tanycytes and GFAP+ cells of the hypothalamus, as well as in Bergmann glia and astrocytes of the cerebellum. Understanding which cell types express Fgfr1 may elucidate its role in neuropsychiatric disorders and brain development.

scholarly journals Quantitative assessment of Fgfr1 expression in neurons and glia

2016 ◽  
Author(s):  
Lisha Choubey ◽  
Jantzen C Collette ◽  
Karen Muller Smith
Keyword(s):  
Glial Cells ◽  
Synapse Formation ◽  
Fluorescent Protein ◽  
Neuropsychiatric Disorders ◽  
Cell Types ◽  
Lipid Binding ◽  
Bergmann Glia ◽  
Radial Glial Cells ◽  
Postnatal Maturation ◽  
Green Fluorescent

Fibroblast growth factors (FGFs) and their receptors (FGFRs) have numerous functions in the developing and adult CNS. For example, the FGFR1 receptor is important for proliferation of radial glial cells in the cortex and hippocampus, oligodendrocyte proliferation and regeneration, midline glia morphology and soma translocation, Bergmann glia morphology, and cerebellar morphogenesis. In addition, FGFR1 signaling in astrocytes is required for postnatal maturation of interneurons expressing parvalbumin (PV). FGFR1 is implicated in synapse formation in the hippocampus, and alterations in the expression of Fgfr1 and its ligand, Fgf2 accompany major depression. Understanding which cell types express Fgfr1 during development may elucidate its roles in normal development of the brain as well as illuminate possible causes of certain neuropsychiatric disorders. Here, we used a BAC transgenic reporter line to trace Fgfr1 expression in the developing murine CNS. The specific transgenic line employed was created by the GENSAT project, tgFGFR1-EGFPGP338Gsat, and includes a gene encoding enhanced green fluorescent protein (EGFP) under the regulation of the Fgfr1 promoter, to trace Fgfr1 expression in the developing CNS. This model reveals that Fgfr1 is primarily expressed in glial cells, in both astrocytes and oligodendrocytes, along with some neurons. Dual labeling experiments indicate that the proportion of GFP+ (Fgfr1+) cells that are also GFAP+ increases from postnatal day 7 (P7) to 1 month, illuminating dynamic changes in Fgfr1 expression during postnatal development of the cortex. In postnatal neurogenic areas, GFP expression was also observed in SOX2, doublecortin (DCX), and brain lipid-binding protein (BLBP) expressing cells. Fgfr1 is also highly expressed in DCX positive cells of the dentate gyrus, but not in the rostral migratory stream. Fgfr1 driven GFP was also observed in tanycytes and GFAP+ cells of the hypothalamus, as well as in Bergmann glia and astrocytes of the cerebellum. Understanding which cell types express Fgfr1 may elucidate its role in neuropsychiatric disorders and brain development.

scholarly journals Subcellular localization of fibroblast growth factor receptor type 2 and correlation with CTNNB1 genotype in adrenocortical carcinoma

2020 ◽  
Author(s):  
Matthias Haase ◽  
Anne Thiel ◽  
Ute I. Scholl ◽  
Hany Ashmawy ◽  
Matthias Schott ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Adrenocortical Carcinoma ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Beta Catenin ◽  
Fibroblast Growth ◽  
Mutational Status ◽  
Cancer Types

Abstract Objective: Fibroblast growth factor receptor (FGFR) 2 regulates the development of the adrenal gland in mice. In addition, FGFR2-mediated signalling has been shown to prevent apoptosis and to enhance proliferation in adrenocortical precursor cells. The activation of the Wingless/Int-1 (WNT) / beta catenin pathway as a key mechanism of adrenocortical tumourigenesis has been linked to FGFR2 signalling in other cell types. Therefore we hypothesised that FGFR2 expression may also play a role in adrenocortical carcinoma (ACC). We conducted a pilot study and analysed protein expression of FGFR2 in 26 ACCs using immunohistochemistry technique. Data on the CTNNB1 mutation status and clinical data were correlated to the expression of FGFR2. Results: We observed a high variability in FGFR2 expression between the different tumour samples. There was a subset of ACC with comparatively high nuclear expression of FGFR2. We did not find a clear association between the CTNNB1 mutational status or clinical features and the FGFR2 expression. We conclude that FGFR signalling plays a role in adrenocortical carcinoma. Our data encourages further investigations of FGFR signalling in ACC, especially since new inhibitors of FGFR signalling are already entering clinical trials for the treatment of other cancer types.

scholarly journals Subcellular localization of fibroblast growth factor receptor type 2 and correlation with CTNNB1 genotype in adrenocortical carcinoma

2020 ◽  
Author(s):  
Matthias Haase ◽  
Anne Thiel ◽  
Ute I. Scholl ◽  
Hany Ashmawy ◽  
Matthias Schott ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Adrenocortical Carcinoma ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Beta Catenin ◽  
Fibroblast Growth ◽  
Mutational Status ◽  
Cancer Types

Abstract Objective: Fibroblast growth factor receptor (FGFR)2 regulates the development of the adrenal gland in mice. In addition, FGFR2-mediated signalling has been shown to prevent apoptosis and to enhance proliferation in adrenocortical precursor cells. The activation of the Wingless/Int-1 (WNT) / beta catenin pathway as a key mechanism of adrenocortical tumourigenesis has been linked to FGFR2 signalling in other cell types. Therefore we hypothesised that FGFR2 expression may also play a role in adrenocortical carcinoma (ACC). We conducted a pilot study and analysed protein expression of FGFR2 in 26 ACCs using immunohistochemistry technique. Data on the CTNNB1 mutation status and clinical data were correlated to the expression of FGFR2. Results: We observed a high variability in FGFR2 expression between the different tumour samples. There was a subset of ACC with comparatively high nuclear expression of FGFR2. We did not find a clear association between the CTNNB1 mutational status or clinical features and the FGFR2 expression. We conclude that FGFR signalling plays a role in adrenocortical carcinoma. Our data encourages further investigations of FGFR signalling in ACC, especially since new inhibitors of FGFR signalling are already entering clinical trials for the treatment of other cancer types.

Divergent fibroblast growth factor signaling pathways in lung fibroblast subsets: where do we go from here?

2015 ◽  
Vol 309 (8) ◽  
pp. L751-L755 ◽  
Author(s):  
Jordi Ruiz-Camp ◽  
Rory E. Morty
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Fibroblast Growth Factor ◽  
Lung Development ◽  
Fluorescent Protein ◽  
Growth Factor Receptor ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Growth Factor Signaling ◽  
Fibroblast Growth

Lung fibroblasts play a key role in postnatal lung development, namely, the formation of the alveolar gas exchange units, through the process of secondary septation. Although evidence initially highlighted roles for fibroblasts in the production and remodeling of the lung extracellular matrix, more recent studies have described the presence of different fibroblast subsets in the developing lung. These subsets include myofibroblasts and lipofibroblasts and their precursors. These cells are believed to play different roles in alveologenesis and are localized to different regions of the developing septa. The precise roles played by these different fibroblast subsets remain unclear. Understanding the signaling pathways that control the discrete functions of these fibroblast subsets would help to clarify the roles and the regulation of lung fibroblasts during lung development. Here, we critically evaluate a recent report that described divergent fibroblast growth factor (FGF) signaling pathways in two different subsets of lung fibroblasts that express different levels of green fluorescent protein (GFP) driven by the platelet-derived growth factor receptor-α promoter. The GFP expression was used as a surrogate for lipofibroblasts (GFPlow) and myofibroblasts (GFPhigh). It was suggested that Fgf10/Fgf1 and Fgf18/Fgfr3 autocrine pathways may be operative in GFPlow and GFPhigh cells, respectively, and that these pathways might regulate the proliferation and migration of different fibroblast subsets during alveologenesis. These observations lay important groundwork for the further exploration of FGF function during normal lung development, as well as in aberrant lung development associated with bronchopulmonary dysplasia.

scholarly journals Satellite glial cells modulate cholinergic transmission between sympathetic neurons

2019 ◽  
Author(s):  
Joana Enes ◽  
Surbhi Sona ◽  
Nega Gerard ◽  
Alexander C. Mitchell ◽  
Marian Haburcak ◽  
...  
Keyword(s):  
Glial Cells ◽  
Neural Control ◽  
Synapse Formation ◽  
Close Contact ◽  
Sympathetic Neurons ◽  
Cell Types ◽  
Sympathetic Neuron ◽  
Sympathetic Ganglia ◽  
Satellite Glial Cells ◽  
Satellite Glia

AbstractPostganglionic sympathetic neurons and satellite glial cells are the two major cell types of the peripheral sympathetic ganglia. Sympathetic neurons project to and provide neural control of peripheral organs and have been implicated in human disorders ranging from cardiovascular disease to peripheral neuropathies. Here we show that satellite glia regulate postnatal development and activity of sympathetic neurons, providing evidence for local ganglionic control of sympathetic drive. We show changes in the cellular architecture of the rat sympathetic ganglia during the postnatal period, with satellite glia enwrapping sympathetic neuronal somata during a period of neuronal hypertrophy. In culture, satellite glia contribute to neuronal survival, promote synapse formation and play a modulatory role in neuron-to-neuron cholinergic neurotransmission, consistent with the close contact seen within the ganglia. Cultured satellite glia make and release neurotrophins, which can partially rescue the neurons from nerve growth factor deprivation. Electrophysiological recordings and immunocytochemical analysis on cultured sympathetic neurons show that satellite glial cells influence synapse number and total neuronal activity with little effect on neuronal intrinsic excitability. Thus, satellite glia play an early and ongoing role within the postnatal sympathetic ganglia, expanding our understanding of the contributions of local and target-derived factors in the regulation of sympathetic neuron function.

scholarly journals Subcellular localization of fibroblast growth factor receptor type 2 and correlation with CTNNB1 genotype in adrenocortical carcinoma

2020 ◽  
Author(s):  
Matthias Haase ◽  
Anne Thiel ◽  
Ute I. Scholl ◽  
Hany Ashmawy ◽  
Matthias Schott ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Adrenocortical Carcinoma ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Beta Catenin ◽  
Fibroblast Growth ◽  
Mutational Status ◽  
Cancer Types

Abstract Objective: Fibroblast growth factor receptor (FGFR)2 regulates the development of the adrenal gland in mice. In addition, FGFR2-mediated signalling has been shown to prevent apoptosis and to enhance proliferation in adrenocortical precursor cells. The activation of the Wingless/Int-1 (WNT) / beta catenin pathway as a key mechanism of adrenocortical tumourigenesis has been linked to FGFR2 signalling in other cell types. Therefore we hypothesised that FGFR2 expression may also play a role in adrenocortical carcinoma (ACC). We conducted a pilot study and analysed protein expression of FGFR2 in 26 ACCs using immunohistochemistry technique. Data on the CTNNB1 mutation status and clinical data were correlated to the expression of FGFR2. Results: We observed a high variability in FGFR2 expression between the different tumour samples. There was a subset of ACC with comparatively high nuclear expression of FGFR2. We did not find a clear association between the CTNNB1 mutational status or clinical features and the FGFR2 expression. We conclude that FGFR signalling plays a role in adrenocortical carcinoma. Our data encourages further investigations of FGFR signalling in ACC, especially since new inhibitors of FGFR signalling are already entering clinical trials for the treatment of other cancer types.

scholarly journals Prenatal Stress Selectively Impairs Neuroligin 1-Dependent Neurogenesis by Suppressing Astrocytic FGF2-Neuronal FGFR1 Axis

2022 ◽  
Author(s):  
Gee Euhn Choi ◽  
Chang Woo Chae ◽  
Mo Ran Park ◽  
Jee Hyeon Yoon ◽  
Young Hyun Jung ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Prenatal Stress ◽  
Synapse Formation ◽  
Growth Factor Receptor ◽  
Induced Pluripotent Stem Cell ◽  
Antibody Array ◽  
Fibroblast Growth ◽  
Induced Pluripotent

Abstract Exposure to maternal stress irreversibly impairs neurogenesis of offspring through inducing life-long effects on interaction between neurons and glia under raging differentiation process, culminating in cognitive and neuropsychiatric abnormalities in adulthood. We identified how prenatal exposure to the stress-hormone glucocorticoid impairs synapse formation and subsequent neurogenesis using human induced pluripotent stem cell (iPSC)-derived neural stem cell (NSC) and ICR mice. Following prenatal glucocorticoid exposure, NSC-derived astrocytes were found to be A1-like neurotoxic astrocytes. Moreover, cortisol-treated astrocyte conditioned media (ACM) then specifically downregulated AMPA receptor-mediated glutamatergic synaptic formation and transmission in differentiating neurons, by inhibiting localization of ionotropic glutamate receptor (GluR) 1/2 into synapses. We revealed that downregulated astrocytic fibroblast growth factor 2 (FGF2) and nuclear fibroblast growth factor receptor 1 (FGFR1) of neurons are key pathogenic factors for reducing glutamatergic synapse formation, according to data from RNA sequencing and antibody array. We further confirmed that cortisol-treated ACM specifically decreased the binding of neuronal FGFR1 to the synaptogenic NLGN1 promoter, but this was reversed by FGFR1 restoration. Upregulation of neuroligin 1, which is important in scaffolding GluR1/2 into the postsynaptic compartment, eventually normalized glutamatergic synaptogenesis and subsequent neurogenesis. Moreover, FGF2 pretreatment of a prenatal corticosterone-exposed mouse elevated neuroligin 1 expression and trafficking of GluR1/2 into the postsynaptic compartment, improving spatial memory and depression/anxiety-like behaviors. In conclusion, we demonstrated that neuroligin 1 restoration by astrocytic FGF2 and its downstream neuronal nuclear FGFR1 as a critical target of prenatal stress-induced glutamatergic synaptogenesis and demonstrated its function in controlling both neurogenesis and hippocampal-related behaviors.

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