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Results for “Fibroblast Growth Factor 10”

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At least 19 recordsLinked to original sources
PubMed2004

Requirement for fibroblast growth factor 10 or fibroblast growth factor receptor 2-IIIb signaling for cecal development in mouse.

Epithelial-mesenchymal interactions are critical for the formation of gastrointestinal buds such as the cecum from the midgut, but the mechanisms regulating this process remain unclear. To investigate this problem, we have studied the temporal and spatial expression of key genes known to orchestrate branching morphogenesis. At E10.5, Fibroblast growth factor 10 (Fgf10) is specifically expressed in the mesenchyme above the future cecal epithelial bud, whereas Fgfr2b is found throughout the gut epithelium. From E11.5 onwards, Fgf10 expression is found throughout the cecum mesenchyme. Other relevant signaling molecules such as Sonic hedgehog, Wnt2b, and Tbx4 transcripts are found throughout the gut epithelium, including the cecum. Epithelial expression is also seen for Sprouty2, but only from E14.5 onwards. By contrast, Bone morphogenetic 4 (Bmp4) and Pitx2 are specifically expressed in the mesenchyme of the cecal bud at E11.5. Abrogation of either Fgf10 or Fgfr2b leads to similar phenotypes characterized by an arrest of epithelial invasion into the cecal mesenchymal tissue. However, a bud of undifferentiated cecal mesenchymal tissue is maintained throughout development. Our results further indicate that mesenchymal FGF10 acts mostly through the epithelial FGFR2b receptor; thereby triggering invasion of the midgut epithelium into the adjacent mesenchyme via an increased rate of epithelial proliferation at the tip of the cecum. Thus, FGF10 signaling via FGFR2b appears to be critical in the extension of the epithelium into the mesenchyme during cecal development.

Actins↗
PubMed1997

Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung.

During mouse lung morphogenesis, the distal mesenchyme regulates the growth and branching of adjacent endoderm. We report here that fibroblast growth factor 10 (Fgf10) is expressed dynamically in the mesenchyme adjacent to the distal buds from the earliest stages of lung development. The temporal and spatial pattern of gene expression suggests that Fgf10 plays a role in directional outgrowth and possibly induction of epithelial buds, and that positive and negative regulators of Fgf10 are produced by the endoderm. In transgenic lungs overexpressing Shh in the endoderm, Fgf10 transcription is reduced, suggesting that high levels of SHH downregulate Fgf10. Addition of FGF10 to embryonic day 11.5 lung tissue (endoderm plus mesenchyme) in Matrigel or collagen gel culture elicits a cyst-like expansion of the endoderm after 24 hours. In Matrigel, but not collagen, this is followed by extensive budding after 48-60 hours. This response involves an increase in the rate of endodermal cell proliferation. The activity of FGF1, FGF7 and FGF10 was also tested directly on isolated endoderm in Matrigel culture. Under these conditions, FGF1 elicits immediate endodermal budding, while FGF7 and FGF10 initially induce expansion of the endoderm. However, within 24 hours, samples treated with FGF10 give rise to multiple buds, while FGF7-treated endoderm never progresses to bud formation, at all concentrations of factor tested. Although exogenous FGF1, FGF7 and FGF10 have overlapping activities in vitro, their in vivo expression patterns are quite distinct in relation to early branching events. We conclude that, during early lung development, localized sources of FGF10 in the mesoderm regulate endoderm proliferation and bud outgrowth.

Animals↗
PubMed2004

Roles of fibroblast growth factor 10 (Fgf10) in adipogenesis in vivo.

The development of white adipose tissue (WAT) of Fgf10-/- mouse embryos was greatly impaired. Here, we examined the mechanism of Fgf10 action in adipogenesis in vivo. The proliferative activity in the WAT of Fgf10-/- embryos was greatly decreased. We also examined the expression of transcription factors, C/EBPbeta, C/EBPalpha and PPARgamma, that are important for adipogenesis. Although the expression of C/EBPbeta and PPARgamma in the WAT of Fgf10-/- embryos was greatly decreased, the expression of C/EBPalpha was essentially unchanged. Therefore, we examined their expression in the WAT of C/EBPalpha-/- embryos. Although the expression of C/EBPbeta and PPARgamma in the WAT was greatly decreased, the expression of Fgf10 was essentially unchanged. As these results in vivo appeared to be contradictory to a transcriptional cascade model in vitro that C/EBPbeta induces the expression of PPARgamma and C/EBPalpha reported, we also examined their expression in the WAT of wild type embryos at different developmental stages. The expression of Fgf10 and C/EBPalpha was followed by that of C/EBPbeta and PPARgamma. The present findings indicate that Fgf10 but not C/EBPalpha is required for the proliferation of preadipocytes. In contrast, both Fgf10 and C/EBPalpha acting synergistically in separate, parallel pathways are required for the differentiation. Unexpectedly, the transcriptional cascade of adipogenesis in vivo described here is distinct from the cascade in vitro previously reported.

Adipocytes↗
PubMed2001

Fibroblast growth factor 10 induces proliferation and differentiation of human primary cultured keratinocytes.

Fibroblast growth factor 10 is a novel member of the fibroblast growth factor family, which is involved in morphogenesis and epithelial proliferation. It is highly homologous to the keratinocyte growth factor (or fibroblast growth factor 7), a key mediator of keratinocyte growth and differentiation. Both fibroblast growth factor 10 and keratinocyte growth factor bind with high affinity to the tyrosine kinase keratinocyte growth factor receptor. Here we analyzed the effect of fibroblast growth factor 10 on primary cultures of human keratinocytes, grown in chemically defined medium, and we compared the proliferative and differentiative cell responses to fibroblast growth factor 10 with those induced by keratinocyte growth factor and epidermal growth factor. Cell counting, 5-bromo-2'-deoxyuridine incorporation, and western blot analysis showed that fibroblast growth factor 10, similarly to keratinocyte growth factor, not only is a potent mitogen for human keratinocytes, but also promotes the expression of both early differentiation markers K1 and K10 and late differentiation marker filaggrin in response to the Ca2+ signal, and seems to sustain the proliferative activity in suprabasal stratified cells. Immunoprecipitation/western blot analysis revealed that fibroblast growth factor 10, similarly to keratinocyte growth factor, is able to induce tyrosine phosphorylation of keratinocyte growth factor receptor and of cellular substrates such as PLCgamma.

Antigens, Differentiation↗
PubMed2002

Requirement of fibroblast growth factor 10 in development of white adipose tissue.

Fibroblast growth factors (FGFs) are important intercellular signaling molecules in developmental processes. Here, we show that FGF10 is secreted by cultured preadipocytes and that prevention of FGF10 signaling inhibits the expression of C/EBPbeta and the subsequent differentiation of these cells. An active form of C/EBPbeta rescued differentiation of the cells in which FGF10 signaling was blocked. Development of white adipose tissue and the expression of C/EBPbeta in this tissue of FGF10 knockout mice were markedly reduced, and the ability of embryonic fibroblasts derived from FGF10 knockout mice to differentiate into adipocytes was impaired. Therefore, FGF10 plays an important role in adipogenesis, at least partly by contributing to the expression of C/EBPbeta through an autocrine/paracrine mechanism.

Adipocytes↗
PubMed2003

Fibroblast growth factor 10 is required for proper development of the mouse whiskers.

Fibroblast Growth Factor (FGF) signaling is known to play an important role during cutaneous development. To elucidate the role of FGF10 during whisker formation, we examined the expression of Fgf10 in normal developing whiskers and phenotypes of Fgf10-deficient whiskers. Fgf10 is first expressed in the maxillary process, lateral and medial nasal processes, then in the mesenchymal cells underneath the future whisker placodes, and in the surrounding mesenchyme of developing whiskers. Fgf10-null whiskers exhibit a significant decrease in number and their structure is disorganized as revealed by scanning electron microscopy. Hair follicle marker genes such as Sonic hedgehog, Patched, and Patched 2 are aberrantly expressed in the mutant whiskers. Thus, FGF10 is required for proper whisker development mediated by SHH signaling in the mouse.

Animals↗
PubMed1997

Mouse fibroblast growth factor 10: cDNA cloning, protein characterization, and regulation of mRNA expression.

Fibroblast growth factor 7 (FGF-7) or keratinocyte growth factor (KGF), is a potent and specific mitogen for epithelial cells. We have recently identified a novel human FGF-7 homologue, named FGF-10. To study the expression of this new FGF family member and its regulation in wound repair, we cloned the mouse FGF-10 (mFGF-10) cDNA. The encoded protein is 92% identical to human FGF-10 and 91% identical to rat FGF-10. When expressed in mammalian 293 cells, the mFGF-10 protein was glycosylated but remained cell- or extracellular matrix-associated. Upon addition of heparin, mFGF-10 protein was released into the media. mRNA encoding mFGF-10 was relatively abundant in lung, skin, brain and heart. In the skin, both FGF-7 and mFGF-10 were expressed in the dermal, but not the epidermal compartment. In contrast to FGF-7, mFGF-10 expression was not induced during cutaneous wound repair. In cultured fibroblasts, expression of mFGF-10 was strongly repressed by transforming growth factor beta and tumor necrosis factor alpha, whereas epidermal growth factor and interleukin-1beta had no effect. These results demonstrate a differential regulation of mFGF-10 and FGF-7 expression in vitro and during the wound healing process.

3T3 Cells↗
PubMed2005

Colonic atresia without mesenteric vascular occlusion. The role of the fibroblast growth factor 10 signaling pathway.

BACKGROUND/PURPOSE: Colonic atresia occurs in 1:20,000 live births, offering a neonatal surgical challenge. Prenatal expression of fibroblast growth factor 10 (Fgf10), acting through fibroblast growth factor receptor 2b (Fgfr2b), is critical to the normal development of the colon. Invalidation of the Fgf10 pathway results in colonic atresia, inherited in an autosomal recessive pattern. Classically, disturbance of the mesenteric vasculature has been thought to cause many forms of intestinal atresia. The purpose of this study was to evaluate the role of vascular occlusion in the pathogenesis of colonic atresia. METHODS: Wild type (Wt), Fgf10(-/-), and Fgfr2b(-/-) mutant mouse embryos were harvested from timed pregnant mothers. Immediately following harvest, filtered India ink was infused via intracardiac microinjection. The gastrointestinal tract was dissected, and photomicrographs of the mesenteric arterial anatomy were taken at key developmental time points. RESULTS: Photomicrographs after India ink microinjections demonstrate normal, patent mesenteric cascades to the atretic colon at the time points corresponding to the failure of colonic development in the Fgf10(-/-) and Fgfr2b(-/-) mutants. The mesenteric arterial anatomy of the colon demonstrates no difference between the Wt and mutant colonic atresia. CONCLUSIONS: The absence of embryonic expression of Fgf10 or its receptor Fgfr2b results in colonic atresia in mice. India ink microinjection is a direct measure of mesenteric arterial patency. Colonic atresia in the Fgf10(-/-) and Fgfr2b(-/-) mutants occurs despite normal mesenteric vascular development. Thus the atresia is not the result of a mesenteric vascular occlusion. The patent colonic mesentery of the Fgf10(-/-) and Fgfr2b(-/-) mutants challenges an accepted pathogenesis of intestinal atresia. Although colonic atresia can occur as a result of vascular occlusion, new evidence exists to suggest that a genetic mechanism may play a role in the pathogenesis of this disease.

Animals↗
PubMed2003

Gene expression of fibroblast growth factors 10 and 7 is downregulated in the lung of nitrofen-induced diaphragmatic hernia in rats.

BACKGROUND/PURPOSE: Newborns with congenital diaphragmatic hernia (CDH) still have a high mortality rate, which has been attributed to pulmonary hypoplasia and pulmonary hypertension. Fibroblast growth factors (FGFs) are essential components of the gene network that regulates lung development. Recent studies suggest that the new member of FGF family, FGF-10, plays a fundamental role in branching morphogenesis and is essential for lung formation. FGF-10-deficient mice exhibit complete absence of lungs. FGF-7 promotes epithelial proliferation and expansion leading to the formation of cystlike structures. The aim of this study was to determine the gene level expression of FGF-10 and FGF-7 in the lung of nitrofen-induced CDH. METHODS: Congenital diaphragmatic hernia (CDH) was induced in pregnant rats after administration of 100 mg of nitrofen on day 9.5 of gestation (term, 22 days). In control animals, the same dose of olive oil was given without nitrofen. Cesarean section was performed on day 21 of gestation. The fetuses were divided into 3 groups: normal controls (n = 16), nitrofen induced without CDH (n = 16), and nitrofen-induced CDH (n = 16). Total RNA and DNA were extracted from the lung in each group and measured. mRNA was extracted from total RNA. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate mRNA expressions of FGF-10 and FGF-7. Levels of mRNA were expressed as a ratio of the band density divided by that of beta-actin, a house-keeping gene. RESULTS: FGF-10 mRNA expression was decreased significantly in CDH lung (2.914 +/- 0.320) compared with controls (4.062 +/- 0.307; P <.05) and nitrofen induced without CDH lung (3.923 +/- 0.250; P <.01). FGF-7 mRNA expression was decreased significantly in CDH lung (0.777 +/- 0.097) compared with controls (1.028 +/- 0.093; P <.01). CONCLUSIONS: Decreased gene expression of FGF-10 and FGF-7 in the hypoplastic lung suggests that pulmonary hypoplasia in nitrofen-induced CDH rat may be caused by reduced synthesis of FGF-10 and FGF-7 during lung morphogenesis.

Animals↗
PubMed2005

Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis.

The pathogenic mechanism underlying the hyperproliferation of keratinocytes in psoriasis is still not completely clarified. The production of cytokines released by activated T lymphocytes infiltrating the upper dermis probably has a crucial role. Even dermal fibroblasts can participate in the process through the secretion of growth factors, and some studies have reported an increased expression of the insulin-like growth factor 1. Few studies, however, have focused on the possible involvement of the keratinocyte growth factor (KGF/FGF-7) and the fibroblast growth factor 10 (FGF-10/KGF-2), which are secreted by fibroblasts and stimulate keratinocyte proliferation acting through a receptor specifically expressed by epithelial cells. The aim of this study was to investigate the expression of KGF and FGF-10 on the skin of patients with psoriasis by immunohistochemical analysis and to evaluate the correlation with the lymphocyte infiltrate and the epidermal proliferation. Immunostaining for KGF and FGF-10 showed that both the growth factors are upregulated in the upper dermis of psoriatic skin, and that the expression is correlated with the presence of T-cell infiltrate and with keratinocyte proliferation. Our data suggest that in psoriatic lesions activated lymphocytes can stimulate fibroblasts to produce KGF and FGF-10, which in turn contribute to sustain the hyperproliferative status of the keratinocytes.

Adult↗
PubMed2005

Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands.

Autosomal dominant aplasia of lacrimal and salivary glands (ALSG; OMIM 180920 and OMIM 103420) is a rare condition characterized by irritable eyes and dryness of the mouth. We mapped ALSG to 5p13.2-5q13.1, which coincides with the gene fibroblast growth factor 10 (FGF10). In two extended pedigrees, we identified heterozygous mutations in FGF10 in all individuals with ALSG. Fgf10(+/-) mice have a phenotype similar to ALSG, providing a model for this disorder. We suggest that haploinsufficiency for FGF10 during a crucial stage of development results in ALSG.

Animals↗
PubMed2004

Fibroblast growth factor 10 (Fgf10) invalidation results in anorectal malformation in mice.

BACKGROUND/PURPOSE: Anorectal malformations occur in 1 per 4,000 live births and represent a surgical challenge. Although critically important, the basic mechanisms of normal anorectal union are incompletely understood. Fgf10 signaling is known to serve a key role in mesenchymal/epithelial interactions in many organ systems including the gastrointestinal tract (GIT). The authors therefore hypothesized that Fgf10 signaling has a central role in normal anorectal development. METHODS: Fgf10 expression in wild-type (Wt) embryos was evaluated using whole-mount in situ hybridization. Wt and Fgf10-/- embryos were harvested from timed pregnant mothers at E12.5 through E17.5 and were analyzed for anorectal phenotype. RESULTS: Wt development of union between anorectal structures is completed between E12.5 and E13.5 with luminal communication between distal rectal epithelium and anus. Fgf10 is discretely expressed at E12.5 in the distal rectum. Fgf10-/- mutants show failure of union of the rectum and anus at an early stage (E13.5) and near term (E17.5). CONCLUSIONS: Fgf10 is expressed in the rectum at the time when anorectal continuity is established, indicating a role in normal anorectal development. Fgf10 invalidation (Fgf10-/- mutant) results in a genetically reproducible anorectal malformation phenotype. Fgf10 function is critical for normal anorectal development.

Anal Canal↗
PubMed2006

Fibroblast growth factor 10 is required for survival and proliferation but not differentiation of intestinal epithelial progenitor cells during murine colon development.

Epithelial-mesenchymal interactions that govern the development of the colon from the primitive gastrointestinal tract are still unclear. In this study, we determine the temporal-spatial expression pattern of Fibroblast growth factor 10 (Fgf10), a key developmental gene, in the colon at different developmental stages. We found that Fgf10 is expressed in the mesenchyme of the distal colon, while its main receptor Fgfr2-IIIb is expressed throughout the entire intestinal epithelium. We demonstrate that Fgf10 inactivation leads to decreased proliferation and increased cell apoptosis in the colonic epithelium at E10.5, therefore resulting in distal colonic atresia. Using newly described Fgf10 hypomorphic mice, we show that high levels of FGF10 are dispensable for the differentiation of the colonic epithelium. Our work unravels for the first time the pivotal role of FGF10 in the survival and proliferation of the colonic epithelium, biological activities which are essential for colonic crypt formation.

Animals↗
PubMed2004

Retinoic acid selectively regulates Fgf10 expression and maintains cell identity in the prospective lung field of the developing foregut.

Although respiratory tract defects that result from disruption of retinoic acid (RA) signaling have been widely reported, the mechanism by which endogenous RA regulates early lung morphogenesis is unknown. Here, we provide novel evidence that a major role for RA is to selectively maintain mesodermal proliferation and induce fibroblast growth factor 10 (Fgf10) expression in the foregut region where the lung forms. By using a pan-RAR antagonist (BMS493) in foregut explant cultures, we show that bud initiation is selectively blocked in the prospective respiratory region by failure to induce Fgf10 in the corresponding mesoderm. The RA regulation of Fgf10 expression occurs only in this region, within a defined developmental window, and is not seen in other foregut derivatives such as thyroid and pancreas where Fgf10 is also required for normal development. Furthermore, we show that RA activity is essential in the lung field to maintain lung cell identity in the endoderm; RAR antagonism disrupts expression of thyroid transcription factor 1 (Ttf1), an early marker of the respiratory region in the endoderm, and surfactant protein C (Sp-C) mRNAs. Our observations in mouse foregut cultures are corroborated by data from an in vivo model of vitamin A deficiency in rats. Our study supports RA as an essential regulator of gene expression and cellular activities during primary bud formation.

Animals↗
PubMed1999

KGF and FGF-10 stimulate liquid secretion in human fetal lung.

During fetal life, the pulmonary epithelium secretes liquid that distends the airways and is important for normal lung growth and development. The factors regulating human fetal lung liquid secretion are poorly understood; however, recent studies in murine models show that keratinocyte growth factor (KGF, FGF-7) and fibroblast growth factor 10 (FGF-10) stimulate liquid secretion. We asked whether KGF and FGF-10 stimulate liquid secretion in human fetal lung. First trimester fetal lung explants developed dose-dependent increases in intraluminal volume in response to KGF and FGF-10. Although there were no acute changes in explant transepithelial potential difference in response to KGF (0.1-1000 ng/mL), exposure to 5-50 ng/mL KGF over 60 h depolarized transepithelial potential difference compared with controls. We used ribonuclease protection assays to quantitate the ontogeny and regulation of mRNA expression for KGF and its receptor. Both mRNA were expressed in fetal and postnatal lung. Because the promoter region of the human KGF gene contains cAMP and IL-6 response elements, we asked whether cAMP or IL-6 stimulated expression of KGF or its receptor. We have previously shown that cAMP stimulates liquid secretion in this model. Both cAMP and IL-6 significantly increased expression of KGF but not KGF receptor during a 48-h experiment. Thus, stimulation of liquid secretion in explant models by cAMP may be mediated in part by induction of KGF expression. KGF and FGF-10 may be important paracrine factors regulating liquid secretion in human fetal lung.

Antigen-Antibody Reactions↗