Atrial natriuretic peptide type C induces a cell-cycle switch from proliferation to differentiation in brain-derived neurotrophic factor- or nerve growth factor-primed olfactory receptor neurons.
With the discovery of postnatal stem cells within the brain, it has become important to understand how extracellular factors might affect the maturation of neuronal precursors in the postnatal brain. Neurotrophic factors are known to play a role in neuronal development but display pleiotrophic effects, in part because of their physiological interactions with other factors. One factor positioned to interact with neurotrophins in the brains of postnatal animals is atrial C-type natriuretic peptide (CNP). In this study, we used olfactory receptor neurons (ORNs) as a model, because their precursors demonstrate the most robust and functional postnatal neurogenesis of those systems thus far described. We examined the effects of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) and the interactions of these neurotrophins and CNP in postnatal olfactory neuronal precursors. Results obtained using mice with targeted deletion of the gene for BDNF indicated that BDNF is a neuroproliferation-inducing and survival factor for ORN precursors. These roles were confirmed in vitro using primary cultures of ORNs. NGF was found to be a proliferation-inducing factor but not a survival factor. The addition of CNP to either BDNF- or NGF-treated neuronal precursors resulted in an inhibition of proliferation and the promotion of maturation. These effects were accompanied by changes in cell-cycle proteins that suggest possible mechanisms for these effects. Thus, CNP may function in the postnatal brain to regulate the exit from the cell cycle in neuronal precursor cells.
Simpson
P Jeanette
PJ
Departments of Neuroscience and Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Miller
Ian
I
Moon
Cheil
C
Hanlon
Andrea L
AL
Liebl
Daniel J
DJ
Ronnett
Gabriele V
GV
D000818:Animals; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors*; D009833:Olfactory Pathways / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D018797:Cell Cycle Proteins; D011956:Receptors, Cell Surface; C414616:guanyl cyclase-B receptor; D020098:Natriuretic Peptide, C-Type; D020932:Nerve Growth Factor; D020928:Mitogen-Activated Protein Kinases; D006152:Cyclic GMP