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(Circulation Research. 2002;90:e5.)
© 2002 American Heart Association, Inc.

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FGF2 Signaling Is Required for the Development of Neuronal Circuits Regulating Blood Pressure

Rosanna Dono^*, Jörg Faulhaber^*, Antonella Galli, Aimée Zuniga, Tilmann Volk, Gemma Texido, Rolf Zeller, Heimo Ehmke

From the Department of Developmental Biology (R.D., A.G., A.Z., R.Z.), Faculty of Biology, Utrecht University, Utrecht, The Netherlands; Institut für Physiologie (J.F., T.V., H.E.), Universität Hamburg, Martinistraße 52, D-20246 Hamburg, Germany; and European Molecular Biology Laboratories (G.T.), Heidelberg, Germany. Present address for G.T. is the Department of Pharmacology, Pharmacia and Upjohn, Nerviano, Italy.

Correspondence and request for material to Prof Dr H. Ehmke, Institut für Physiologie, Universität Hamburg, Martinistraße 52, D-20246 Hamburg, Germany. E-mail ehmke{at}uke.uni-hamburg.de; or Dr Rosanna Dono, Dept of Developmental Biology, Utrecht University, Padualaan 8, NL-3584CH Utrecht, The Netherlands. E-mail r.dono@bio.uu.nl

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.

Key Words: blood pressure • fibroblast growth factor-2 • hypotension • mouse • transgenic

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