This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Google Scholar Articles by Müller, D. Articles by Middendorff, R. PubMed PubMed Citation Articles by Müller, D. Articles by Middendorff, R.

Expression of Guanylyl Cyclase (GC)-A and GC-B during Brain Development: Evidence for a Role of GC-B in Perinatal Neurogenesis

Institute of Anatomy and Cell Biology (D.M., B.H., R.M.), Justus-Liebig-University, 35385 Giessen, Germany; Institute for Hormone and Fertility Research (G.G.), University of Hamburg, 20251 Hamburg, Germany; Department of Pharmacology (R.C.S.), University of Mississippi, University, Mississippi 38677; and Cold Spring Harbor Laboratory (T.V.M., G.E.), Cold Spring Harbor, New York 11724

Address all correspondence and requests for reprints to: Dr. Dieter Müller, Institute of Anatomy and Cell Biology, Justus-Liebig-University, Aulweg 123, 35385 Giessen, Germany. E-mail: hans-dieter.mueller{at}anatomie.med.uni-giessen.de.

Atrial (ANP) and C-type (CNP) natriuretic peptide generate physiological effects via selective activation of two closely related membrane receptors with guanylyl cyclase (GC) activity, known as GC-A and GC-B. As yet, however, the discrete roles for ANP/GC-A vs. CNP/GC-B signaling in many mammalian tissues are still poorly understood. We here used receptor affinity labeling and GC assays to characterize comparatively GC-A/GC-B expression and functional activity during rat brain development. The study revealed that GC-B predominates in the developing and GC-A in the adult brain, with regional differences each between cerebral cortex, cerebellum, and brain stem. Whereas GC-A levels nearly continuously increase between embryonal d 18 and adult, GC-B expression in brain is highest and widely distributed around postnatal d 1. The striking perinatal GC-B peak coincides with elevated expression of nestin, a marker protein for neural stem/progenitor cells. Immunohistochemical investigations revealed a cell body-restricted subcellular localization of GC-B and perinatal abundance of GC-B-expressing cells in regions high in nestin-expressing cells. However, and supported by examination of nestin-GFP transgenic mice, GC-B and nestin are not coexpressed in the same cells. Rather, GC-B⁺ cells are distinguished by expression of NeuN, an early marker of differentiating neurons. These findings suggest that GC-B⁺ cells represent neuronal fate-specific progeny of nestin⁺ progenitors and raise the attention to specific and pronounced activities of CNP/GC-B signaling during perinatal brain maturation. The absence of this activity may cause the neurological disorders observed in GC-B-deficient mice.