Expression analysis of a novel p75(NTR) signaling protein, which regulates cell cycle progression and apoptosis.
Neurotrophin receptor-interacting MAGE (NRAGE) is the most recently identified p75 neurotrophin receptor (p75(NTR)) intracellular binding protein. Previously, NRAGE over-expression was shown to mediate cell cycle arrest and facilitate nerve growth factor (NGF) dependent apoptosis of sympathetic neuroblasts in a p75(NTR) specific manner. Here we have examined the temporal and spatial expression patterns of NRAGE over the course of murine embryogenesis to determine whether NRAGE's expression is consistent with its proposed functions. We demonstrate that NRAGE mRNA and protein are expressed throughout embryonic and adult tissues. The mRNA is constitutively expressed within each tissue across development. However, expression of NRAGE protein displays a tight temporal tissue specific regulation. During early CNS development, NRAGE protein is expressed throughout the neural tube, but by later stages of neurogenesis, NRAGE protein is restricted within the ventricular zone, subplate and cortical plate. Moreover, NRAGE protein expression is limited to proliferative neural subpopulations as we fail to detect NRAGE expression co-localized with mature/differentiation associated neuronal markers. Interestingly, NRAGE's expression is not restricted solely to areas of p75(NTR) expression suggesting that NRAGE may mediate proliferation and/or apoptosis from other environmental signals in addition to NGF within the CNS. Our data support previously characterized roles for NRAGE as a mediator of precursor apoptosis and a repressor of cell cycle progression in neural development.
The Laboratory of Neural Stem Cell Biology, The John P Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada N6A 5K8.
Stephen E
SE
Kendall
Donna E
DE
Goldhawk
Chris
C
Kubu
Philip A
PA
Barker
Joseph M
JM
Verdi
D000818:Animals; D000951:Antigens, Neoplasm; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins; D009420:Nervous System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity; D014018:Tissue Distribution
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C120897:MAGED1 protein, human; C486541:Maged1 protein, mouse; C486542:Maged1 protein, rat; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor