title: FGF2 signaling is required for the development of neuronal circuits regulating blood pressure.
abstract: Fibroblast growth factor 2 (FGF2) signaling is involved in angiogenesis, vascular contractility, and cardiac hypertrophy. Mice lacking a functional FGF2 gene (FGF2(-/-)) are hypotensive, but the primary physiological role of FGF2 in cardiovascular homeostasis remained unknown. Using a chicken FGF2 (cFGF2) transgene under control of the Wnt-1 promotor, we selectively re-expressed FGF2 in the developing nervous system of FGF2(-/-) (transgenic FGF2 mutant) embryos. Expression of the cFGF2 transgene in the developing nervous system, including its autonomic region, was limited to the period between embryonic day 9.5 and 14.5. Significantly, no FGF2 re-expression was detected in developing heart and blood vessels. Pharmacological analysis revealed a normalization of the blood pressure response to isoproterenol-induced vasodilation in adult transgenic FGF2 mutant mice. In addition, the hypotensive phenotype was rescued in 1 line (of 2) transgenic FGF2 mutant adult mice having expressed higher levels of cFGF2 proteins during nervous system development. These genetic studies indicate that FGF2 signaling is essential for complete development of the neural circuitry required for central regulation of blood pressure, whereas it appears dispensable for blood pressure control in the healthy adult. The full text of this article is available at http://www.circresaha.org.
authors.affiliation: Department of Developmental Biology, Faculty of Biology, Utrecht University, Utrecht, The Netherlands. r.dono@bio.uu.nl
authors.forename: Rosanna
authors.initials: R
authors.lastname: Dono
authors.forename: Jörg
authors.initials: J
authors.lastname: Faulhaber
authors.forename: Antonella
authors.initials: A
authors.lastname: Galli
authors.forename: Aimée
authors.initials: A
authors.lastname: Zuniga
authors.forename: Tilmann
authors.initials: T
authors.lastname: Volk
authors.forename: Gemma
authors.initials: G
authors.lastname: Texido
authors.forename: Rolf
authors.initials: R
authors.lastname: Zeller
authors.forename: Heimo
authors.initials: H
authors.lastname: Ehmke
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002645:Chickens; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006339:Heart Rate / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009154:Mutation; D009420:Nervous System / Q000196:embryology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016222:Fibroblast Growth Factor 2