Neurofibromin and Neuronal Apoptosis
Abstract
During development, neurons become dependent on target-derived neurotrophins tor survival and maintenance of differentiated functions. Failed or inappropriate target interactions in vivo, or withdrawal of neurotrophins in vitro, lead to a characteristic sequence of molecular cell death events termed "apoptosis". The purpose of the proposed research is to examine the roles of the Nf1 gene product, neurofibromin, in modulating the apoptotic response to neurotrophin withdrawal, as well as the survival response to depolarization. Over the past year, comparisons of the responses of Nf1+/-(haploinsufficient)and Nf1+/+ mouse sensory and sympathetic neurons, isolated from several different embryonic stages, to neurotrophin- and activity-mediated survival signaling were completed. Nf1 haploinsufficient neurons are more sensitive to suboptimal neurotrophin doses and depolarization, and survive longer after nerve growth factor is withdrawn. In addition, the effects of NGF exposure on the acquisition of neurotrophin dependence by Nf1-/- and Nf1+/- sensory and sympathetic neurons was examined, using cells isolated from early (E12) mouse embryos. Although neurofibromin-deficient neurons are sensitive to certain apoptotic stimuli (e.g. C2-ceramide), they are resistant to other signals for programmed cell death. The jun kinase/ c-jun pathway may be involved in this resistance to apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA444243
Entities
People
- Kristine S. Vogel
Organizations
- University of Texas Health Science Center at San Antonio