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

Muller, D., Hida, B., Guidone, G., Speth, R. C., Michurina, T. V., Enikolopov, G. N., Middendorff, R. (October 2009) Expression of Guanylyl Cyclase (GC)-A and GC-B during Brain Development: Evidence for a Role of GC-B in Perinatal Neurogenesis. Endocrinology, 150 (12). pp. 5520-5529. ISSN 0013-7227

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Abstract

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.

Item Type: Paper
Uncontrolled Keywords: NATRIURETIC-PEPTIDE RECEPTOR CENTRAL-NERVOUS-SYSTEM NEURONAL MARKER NEUN NEURAL STEM-CELLS PROGENITOR CELLS LEYDIG-CELLS NESTIN MICE PRECURSORS PROTEIN
Subjects: Investigative techniques and equipment
organs, tissues, organelles, cell types and functions > organs types and functions > brain
organism description > animal > developmental stage > child
organism description > animal > developmental stage
organs, tissues, organelles, cell types and functions > organs types and functions
organs, tissues, organelles, cell types and functions
CSHL Authors:
Communities: CSHL labs > Enikopolov lab
CSHL Cancer Center Shared Resources > Animal Services
Depositing User: Matt Covey
Date: 16 October 2009
Date Deposited: 21 Feb 2013 16:30
Last Modified: 29 Dec 2014 19:43
Related URLs:
URI: https://repository.cshl.edu/id/eprint/27373

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