scholarly journals Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 753-765 ◽  
Author(s):  
X. Xu ◽  
M. Weinstein ◽  
C. Li ◽  
M. Naski ◽  
R.I. Cohen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptor ◽  
Limb Bud ◽  
Fibroblast Growth ◽  
Reciprocal Regulation ◽  
Fusion Junction ◽  
High Affinity Receptor ◽  
Membrane Spanning ◽  
Domain Iii

FGFR2 is a membrane-spanning tyrosine kinase that serves as a high affinity receptor for several members of the fibroblast growth factor (FGF) family. To explore functions of FGF/FGFR2 signals in development, we have mutated FGFR2 by deleting the entire immunoglobin-like domain III of the receptor. We showed that murine FGFR2 is essential for chorioallantoic fusion and placenta trophoblast cell proliferation. Fgfr2(DeltaIgIII/DeltaIgIII) embryos displayed two distinct defects that resulted in failures in formation of a functional placenta. About one third of the mutants failed to form the chorioallantoic fusion junction and the remaining mutants did not have the labyrinthine portion of the placenta. Consequently, all mutants died at 10–11 days of gestation. Interestingly, Fgfr2(DeltaIgIII/DeltaIgIII) embryos do not form limb buds. Consistent with this defect, the expression of Fgf8, an apical ectodermal factor, is absent in the mutant presumptive limb ectoderm, and the expression of Fgf10, a mesenchymally expressed limb bud initiator, is down regulated in the underlying mesoderm. These findings provide direct genetic evidence that FGF/FGFR2 signals are absolutely required for vertebrate limb induction and that an FGFR2 signal is essential for the reciprocal regulation loop between FGF8 and FGF10 during limb induction.

117 FIBROBLAST GROWTH FACTOR RECEPTOR-1c, -2c, -3c, and -4 mRNA ABUNDANCE IN GRANULOSA CELLS DURING FOLLICULAR GROWTH IN CATTLE

2017 ◽  
Vol 29 (1) ◽  
pp. 167
Author(s):  
L. F. Schütz ◽  
L. Zhang ◽  
B. C. Morrell ◽  
N. B. Schreiber ◽  
C. Cortinovis ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Granulosa Cells ◽  
Growth Factor Receptor ◽  
Mrna Abundance ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors ◽  
Genes Encoding ◽  
Mrna Extraction ◽  
Domain Iii

Fibroblast growth factors (FGF) regulate folliculogenesis of several species, including cattle. The cellular responses to a particular FGF are influenced by the diversity of high affinity fibroblast growth factor receptors (FGFR). There are 4 distinct genes encoding FGFR in vertebrates and the occurrence of mRNA splicing in the immunoglobulin-like domain III generates a diversity of sequences, and results in various isoforms of FGFR1, FGFR2, and FGFR3 (but not of FGFR4). Because FGFR have different ligand specificities, the presence of FGFR in bovine antral follicles is of fundamental importance for the FGF to exert their effects in the ovary. Hence, the objective of this study was to determine if FGFR1c, FGFR2c, FGFR3c, and FGFR4 mRNA abundance in granulosa cells (GC) change according to follicular size, steroidogenic status, and days post-ovulation during growth of first-wave dominant follicles in cattle. Oestrous cycles of non-lactating dairy cattle were synchronized and ovaries were collected on either Day 3–4 (n = 8) or Day 5–6 (n = 8) post-ovulation (as assessed by rectal ultrasonography). Follicular fluid (FFL) was aspirated from small (1–5 mm), medium (5.1–8 mm), or large (8.1–18 mm) follicles for measurement of oestradiol (E2) and progesterone (P4) levels by radioimmunoassay, and GC were collected for mRNA extraction. Relative quantity of target gene mRNA was expressed as 2−ΔΔCt using the comparative threshold cycle (Ct) method. Data were transformed to natural log (x + 1), to correct for heterogeneity of variance, and analysed via factorial ANOVA with the general linear model procedure of SAS and are reported as least squares means ± s.e.M. Follicle group (based on steroidogenic status and size of follicles), but not days post-ovulation or their interaction, significantly affected FGFR1c, FGFR2c, and FGFR3c mRNA abundance, whereas FGFR4 mRNA abundance was not affected by follicle group or days post-ovulation. FGFR1c mRNA abundance was greater (P < 0.01) in large (44.8 ± 11.3; n = 29), medium (63.8 ± 7.6; n = 64), and small (44.6 ± 11.2; n = 29) E2-inactive (FFL E2/P4 ratio < 1) than in large E2-active (FFL E2/P4 ratio > 1) follicles (10.5 ± 15.5; n = 16) and greater (P < 0.05) in medium E2-inactive than in large and small E2-inactive follicles. FGFR2c mRNA abundance was greater (P < 0.01) in large (423.9 ± 131.9), medium (585.8 ± 97.0), and small (273.6 ± 143.2) E2-inactive than in large E2-active (56.2 ± 195.6) follicles. The FGFR3c mRNA abundance was greater (P < 0.05) in large (143.4 ± 40.2) and medium (160.2 ± 29.3) E2-inactive than in large E2-active (43.2 ± 58.6) follicles and tended to be greater (P = 0.06) in small E2-inactive (101.9 ± 42.9) than in large E2-active follicles. Taken together, the findings that FGFR1c, FGFR2c, and FGFR3c mRNA abundance is lower in GC of E2-active follicles during growth of the first dominant follicle support an anti-differentiation role for these FGFR as well as support the idea that some FGF may regulate the selection of dominant follicles in cattle.

scholarly journals The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain.

1991 ◽  
Vol 11 (9) ◽  
pp. 4627-4634 ◽  
Author(s):  
D E Johnson ◽  
J Lu ◽  
H Chen ◽  
S Werner ◽  
L T Williams
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
The Third ◽  
Immunoglobulin Domain ◽  
Membrane Spanning ◽  
Polyadenylation Signals ◽  
Distinct Membrane

To determine the mechanisms by which multiple forms of fibroblast growth factor (FGF) receptors are generated, we have mapped the arrangement of exons and introns in the human FGF receptor 1 (FGFR 1) gene (flg). We found three alternative exons encoding a portion of the third immunoglobulin (Ig)-like domain of the receptor. One of these alternatives encodes a sequence that is part of a secreted form of FGFR 1. The other two encode sequences that are likely part of transmembrane forms of FGFR 1. One of these forms has not been previously reported in published cDNAs. Also, we have determined the structural organization of a portion of the human FGFR 2 gene (bek) and found a similar arrangement of alternative exons for the third Ig-like domain. The arrangement of these genes suggests that there are conserved mechanisms governing the expression of secreted FGF receptors as well as the expression of at least two distinct membrane-spanning forms of the FGF receptors. The diverse forms appear to be generated by alternative splicing of mRNA and selective use of polyadenylation signals.

scholarly journals Enhanced signaling and morphological transformation by a membrane-localized derivative of the fibroblast growth factor receptor 3 kinase domain.

1997 ◽  
Vol 17 (10) ◽  
pp. 5739-5747 ◽  
Author(s):  
M K Webster ◽  
D J Donoghue
Keyword(s):  
Plasma Membrane ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Fibroblast Growth ◽  
Morphological Transformation ◽  
Cell Proliferation And Differentiation ◽  
Promoter Construct ◽  
Membrane Spanning

Fibroblast growth factor (FGF) receptors (FGFRs) are membrane-spanning tyrosine kinase receptors that mediate regulatory signals for cell proliferation and differentiation in response to FGFs. We have previously determined that the Lys650-->Glu mutation in the activation loop of the kinase domain of FGFR3, which is responsible for the lethal skeletal dysplasia thanatophoric dyplasia type II (TDII), greatly enhances the ligand-independent kinase activity of the receptor. Here, we demonstrate that expression of this construct induces a c-fos promoter construct approximately 10-fold but does not lead to proliferation or morphological transformation of NIH 3T3 cells. In contrast, the isolated kinase domain of activated FGFR3, targeted to the plasma membrane by a myristylation signal, is able to stimulate c-fos expression by 40-fold, induce proliferation of quiescent cells, and morphologically transform fibroblasts. This result suggests that the extracellular and transmembrane domains of FGFRs exert a negative regulatory influence on the activity of the kinase domain. Targeting of the activated kinase domain to either the cytoplasm or the nucleus does not significantly affect biological signaling, suggesting that signals from FGFR3 resulting in mitogenesis originate exclusively from the plasma membrane. Furthermore, our novel observation that expression of a highly activated FGFR3 kinase domain is able to morphologically transform fibroblasts suggests that dysregulation of FGFR3 has the potential to play a role in human neoplasia.

The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain

1991 ◽  
Vol 11 (9) ◽  
pp. 4627-4634
Author(s):  
D E Johnson ◽  
J Lu ◽  
H Chen ◽  
S Werner ◽  
L T Williams
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
The Third ◽  
Immunoglobulin Domain ◽  
Membrane Spanning ◽  
Polyadenylation Signals ◽  
Distinct Membrane

To determine the mechanisms by which multiple forms of fibroblast growth factor (FGF) receptors are generated, we have mapped the arrangement of exons and introns in the human FGF receptor 1 (FGFR 1) gene (flg). We found three alternative exons encoding a portion of the third immunoglobulin (Ig)-like domain of the receptor. One of these alternatives encodes a sequence that is part of a secreted form of FGFR 1. The other two encode sequences that are likely part of transmembrane forms of FGFR 1. One of these forms has not been previously reported in published cDNAs. Also, we have determined the structural organization of a portion of the human FGFR 2 gene (bek) and found a similar arrangement of alternative exons for the third Ig-like domain. The arrangement of these genes suggests that there are conserved mechanisms governing the expression of secreted FGF receptors as well as the expression of at least two distinct membrane-spanning forms of the FGF receptors. The diverse forms appear to be generated by alternative splicing of mRNA and selective use of polyadenylation signals.

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