Neurotrophin-3 signaling maintains maturational homeostasis between neuronal populations in the olfactory epithelium.
Neurons within the olfactory system undergo functional turnover throughout life. This process of cell death and compensatory neurogenesis requires feedback between neuronal populations of different developmental ages. We examined the role of NT-3 in this process. NT-3 was localized within both the olfactory bulb and olfactory epithelium. Mice null for NT-3 showed increased numbers of immature neurons, without change in the number of mature neurons. This was due to compensatory alterations in apoptosis of mature and immature neuronal populations. Using a primary olfactory neuronal culture, NT-3 was found to directly activate the PI3K/Akt pathway and indirectly activate the MAPK and PLC pathways. Activated PI3K/Akt promoted mature neuronal survival and induced the release of secondary factors, which activated the MAPK and PLC pathways to reduce neuronal precursor proliferation and inhibit neuronal maturation. These effects of NT-3 serve to maintain homeostasis between neuronal populations within the olfactory epithelium.
Simpson
P Jeanette
PJ
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Wang
Eugene
E
Moon
Cheil
C
Matarazzo
Valéry
V
Cohen
Deborah R S
DR
Liebl
Daniel J
DJ
Ronnett
Gabriele V
GV
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000172:deficiency* / Q000235:genetics; D009831:Olfactory Mucosa / Q000254:growth & development* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D010738:Type C Phospholipases / Q000378:metabolism / Q000502:physiology
D020933:Neurotrophin 3; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D010738:Type C Phospholipases