But alternatively it could be interpreted as trk

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but alternatively, it could be interpreted as Trk-facilitated signal- ing through p75NTR. Role of P75NTR in vivo The in vitro results presented here suggest that p75NTR plays a role in subplate neuron survival in vivo . Consistent with this hypothesis, p75NTR expression by subplate neurons is high dur- ing the period when they are alive and functioning in cortical circuits and then is downregulated just before their death in vivo (Allendoerfer et al., 1990; Meinecke and Rakic, 1993). Because only subplate neurons, and not cortical neurons, express p75NTR, this could be an elegant mechanism whereby one class of cortical neurons can be selectively eliminated from a cellular environment shared by all. However, preliminary experiments have not revealed an increased loss of subplate neurons in mice with the p75NTR gene knocked out (our unpublished observa- tions), which suggests that subplate survival is controlled by multiple tropic factor receptors. One possible candidate is NT3, because, as shown in Figure 1, subplate neurons express the NT3-specific receptor, TrkC. In support of this hypothesis, we have found that NT3-dependent subplate neuron survival in vitro is only blocked by a combination of K252a and anti-p75NTR antibodies and not by either reagent alone (our unpublished observations). Thus, whereas BDNF requires the p75NTR sig- naling pathway to promote survival, NT3 can signal through either Trk (likely TrkC) or p75NTR. Although our study is of subplate neurons in vitro , these results imply that a novel p75NTR signaling pathway contributes to subplate neuron survival in vivo . Another cortical neuron popu- lation that expresses p75NTR in maturity are the basal forebrain cholinergic neurons (Woolf et al., 1989). These neurons are dependent on p75NTR for survival and are lost in neurodegen- erative diseases, such as Alzheimer’s disease (Geula, 1998; Peter- son et al., 1999). Our observations here raise the possibility that these CNS neurons, like subplate neurons, use this p75NTR signaling pathway for survival in vivo . Thus, activation of this sphingolipid signaling pathway might provide a useful therapeutic approach for rescuing these neurons. REFERENCES Alca´ntara S, Frise´n J, del Rı´o JA, Soriano E, Barbacid M, Silos-Santiago I (1997) TrkB signaling is required for postnatal survival of CNS neurons and protects hippocampal and motor neurons from axotomy- induced cell death. J Neurosci 17:3623–3633. Allendoerfer KL, Shatz CJ (1994) The subplate, a transient neocortical structure: its role in the development of connections between thalamus and cortex. Annu Rev Neurosci 17:185–218. Allendoerfer KL, Shelton DL, Shooter EM, Shatz CJ (1990) Nerve growth factor receptor immunoreactivity is transiently associated with the subplate neurons of the mammalian cerebral cortex. Proc Natl Acad Sci USA 87:187–190.
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