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Differential expression of VEGF isoforms in mouse during development and in the adult
Author(s) -
Ng Y.S.,
Rohan R.,
Sunday M.E.,
Demello D.E.,
D'Amore P.A.
Publication year - 2001
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/1097-0177(2000)9999:9999<::aid-dvdy1093>3.0.co;2-d
Subject(s) - gene isoform , biology , vascular endothelial growth factor , in situ hybridization , microbiology and biotechnology , vascular endothelial growth factor a , gene expression , gene , cancer research , vegf receptors , genetics
Vascular endothelial growth factor (VEGF), a factor that is critical for development of the vascular system in mouse embryos, exists as at least three isoforms, VEGF120, VEGF164, and VEGF188. The isoforms have different affinities for heparan sulfate as well as for the three known VEGF receptors, VEGFR‐1 (Flt‐1), VEGFR‐2 (Flk‐1), and neuropilin‐1, suggesting that different VEGF isoforms may play distinct roles in vascular development. To determine whether there are differences in the organ‐specific expression patterns that would support this concept, we used a quantitative RNase protection assay (RPA) to determine the distribution of different VEGF isoform mRNA in developing and adult mouse organs. Results revealed that the ratios of the three VEGF isoforms changed during organ development and that adult organs expressed different levels of the three VEGF isoforms. Because the lung expressed the highest levels of VEGF188 isoform, we used VEGF isoform‐specific in situ hybridization in the developing lung and determined that type II alveolar epithelial cells were expressing high levels of VEGF188 mRNA. Finally, targeted exon deletion of the VEGF gene revealed that mice that developed in the absence of the heparan sulfate binding isoforms VEGF164 and VEGF188, displayed a variety of vascular defects, including abnormal pulmonary vascular development. Our results support the concept that different VEGF isoforms have distinct functions in vascular development. © 2001 Wiley‐Liss, Inc.