Fibroblast growth factor receptor-1 expression is required for hematopoietic but not endothelial cell development.
OBJECTIVE
The purpose of this study was to clarify the role of fibroblast growth factors (FGFs) and FGF receptors (FGFRs) in hematopoietic/endothelial development.


RESULTS
Using several different FGFR-1-specific antibodies and FGFR-1 promoter-driven LacZ activity, we show that FGFR-1 is expressed and active as a tyrosine kinase in a subpopulation of endothelial cells (approximately 20% of the endothelial pool) during development in embryoid bodies. In agreement, in stem cell-derived teratomas, expression of FGFR-1 was detected in some but not all vessels. The FGFR-1 expressing endothelial cells were mitogenically active in the absence and presence of vascular endothelial growth factor (VEGF). Expression of FGFR-1 in endothelial cell precursors was not required for vascular development, and vascularization was enhanced in FGFR-1-deficient embryoid bodies compared with wild-type stem cells. In contrast, hematopoietic development was severely disturbed, with reduced expression of markers for primitive and definitive hematopoiesis.


CONCLUSIONS
Our data show that FGFR-1 is expressed in early hematopoietic/endothelial precursor cells, as well as in a subpool of endothelial cells in tumor vessels, and that it is critical for hematopoietic but not for vascular development.
Magnusson
Peetra Ulrica
PU
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Ronca
Roberto
R
Dell'Era
Patrizia
P
Carlstedt
Pia
P
Jakobsson
Lars
L
Partanen
Juha
J
Dimberg
Anna
A
Claesson-Welsh
Lena
L
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D007763:Lac Operon; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000502:physiology; D011401:Promoter Regions, Genetic; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D013724:Teratoma / Q000098:blood supply
D051496:Receptor, Fibroblast Growth Factor, Type 1