Expression of guanylyl cyclase (GC)-A and GC-B during brain development: evidence for a role of GC-B in perinatal neurogenesis.
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.
Müller
Dieter
D
Institute of Anatomy and Cell Biology, Justus-Liebig-University, Aulweg 123, 35385 Giessen, Germany. hans-dieter.mueller@anatomie.med.uni-giessen.de
Hida
Balanes
B
Guidone
Gabriela
G
Speth
Robert C
RC
Michurina
Tatyana V
TV
Enikolopov
Grigori
G
Middendorff
Ralf
R
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D001933:Brain Stem / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002531:Cerebellum / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002540:Cerebral Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D015151:Immunoblotting; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D055495:Neurogenesis; D019920:Photoaffinity Labels; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007381:Intermediate Filament Proteins; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D019920:Photoaffinity Labels; D020098:Natriuretic Peptide, C-Type; D049452:Green Fluorescent Proteins; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase