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פותח על ידי קלירמאש פתרונות בע"מ -
The IIIc alternative of Fgfr2 is a positive regulator of bone formation
Year:
2002
Source of publication :
Development
Authors :
מונסונגו-אורנן, אפרת
;
.
פינס, מרק
;
.
Volume :
129
Co-Authors:
Eswarakumar, V.P., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Monsonego-Ornan, E., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Pines, M., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Antonopoulou, I., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Morriss-Kay, G.M., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Lonai, P., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Facilitators :
From page:
3783
To page:
3793
(
Total pages:
11
)
Abstract:
Fibroblast growth factor receptor type 2 (FGFR2) plays major roles in development. Like FGFR1 and FGFR3, it exists as two splice variants, IIIb and IIIc. We have investigated in the mouse the function of FGFR2IIIc, the mesenchymal splice variant of FGFR2 Fgfr2IIIc is expressed in early mesenchymal condensates and in the periosteal collar around the cartilage models; later it is expressed in sites of both endochondral and intramembranous ossification. A translational stop codon inserted into exon 9 disrupted the synthesis of Fgfr2IIIc without influencing the localized transcription of Fgfr2IIIb, the epithelial Fgfr2 variant. The recessive phenotype of Fgfr2IIIc-/- mice was characterized initially by delayed onset of ossification, with continuing deficiency of ossification in the sphenoid region of the skull base. During subsequent stages of skeletogenesis, the balance between proliferation and differentiation was shifted towards differentiation, leading to premature loss of growth, synostosis in certain sutures of the skull base and in the coronal suture of the skull vault, with dwarfism in the long bones and axial skeleton. The retarded ossification was correlated with decrease in the localized transcription of the osteoblast markers secreted phosphoprotein 1 (Spp1) and Runx2/Cbfa1. A decrease in the domain of transcription of the chondrocyte markers Ihh and PTHrP (Pthlh) corresponded with a decrease in their transcripts in the proliferative and hypertrophic chondrocyte zones. These results suggest that Fgfr2IIIc is a positive regulator of ossification affecting mainly the osteoblast, but also the chondrocyte, lineages. This role contrasts with the negative role of Fgfr3, although recent reports implicate FGF18, a ligand for FGFR3IIIc and FGFR2IIIc, as a co-ordinator of osteogenesis via these two receptors.
Note:
Related Files :
Animals
Cell Proliferation
DNA
Female
Male
Mammalia
mice
phenotype
עוד תגיות
תוכן קשור
More details
DOI :
Article number:
0
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
23583
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:00
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Scientific Publication
The IIIc alternative of Fgfr2 is a positive regulator of bone formation
129
Eswarakumar, V.P., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Monsonego-Ornan, E., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Pines, M., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Antonopoulou, I., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Morriss-Kay, G.M., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
Lonai, P., Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
The IIIc alternative of Fgfr2 is a positive regulator of bone formation
Fibroblast growth factor receptor type 2 (FGFR2) plays major roles in development. Like FGFR1 and FGFR3, it exists as two splice variants, IIIb and IIIc. We have investigated in the mouse the function of FGFR2IIIc, the mesenchymal splice variant of FGFR2 Fgfr2IIIc is expressed in early mesenchymal condensates and in the periosteal collar around the cartilage models; later it is expressed in sites of both endochondral and intramembranous ossification. A translational stop codon inserted into exon 9 disrupted the synthesis of Fgfr2IIIc without influencing the localized transcription of Fgfr2IIIb, the epithelial Fgfr2 variant. The recessive phenotype of Fgfr2IIIc-/- mice was characterized initially by delayed onset of ossification, with continuing deficiency of ossification in the sphenoid region of the skull base. During subsequent stages of skeletogenesis, the balance between proliferation and differentiation was shifted towards differentiation, leading to premature loss of growth, synostosis in certain sutures of the skull base and in the coronal suture of the skull vault, with dwarfism in the long bones and axial skeleton. The retarded ossification was correlated with decrease in the localized transcription of the osteoblast markers secreted phosphoprotein 1 (Spp1) and Runx2/Cbfa1. A decrease in the domain of transcription of the chondrocyte markers Ihh and PTHrP (Pthlh) corresponded with a decrease in their transcripts in the proliferative and hypertrophic chondrocyte zones. These results suggest that Fgfr2IIIc is a positive regulator of ossification affecting mainly the osteoblast, but also the chondrocyte, lineages. This role contrasts with the negative role of Fgfr3, although recent reports implicate FGF18, a ligand for FGFR3IIIc and FGFR2IIIc, as a co-ordinator of osteogenesis via these two receptors.
Scientific Publication
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