Expression of and requirement for the NF1 gene product, neurofibromin, during cell differentiation in vivo and in vitro.
dc.contributor.author | Kavka, Amy | en_US |
dc.contributor.advisor | Barald, Kate F. | en_US |
dc.date.accessioned | 2014-02-24T16:23:48Z | |
dc.date.available | 2014-02-24T16:23:48Z | |
dc.date.issued | 1995 | en_US |
dc.identifier.other | (UMI)AAI9610158 | en_US |
dc.identifier.uri | http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9610158 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/104801 | |
dc.description.abstract | When defective, the NF1 tumor suppressor gene causes the disease neurofibromatosis type 1 (NF1), a frequently inherited disorder characterized by numerous benign tumors of the peripheral nervous system. Many of the tissues affected in NF1 are derived from the embryonic neural crest, a migratory population of stem cells which arises during embryogenesis and gives rise to numerous differentiated tissues in the adult. This study outlines the expression of NF1 mRNA and its protein product, neurofibromin, during the time the neural crest arises, migrates, and differentiates, using the embryonic chicken as a model system. We find that while NF1 mRNA is expressed in relatively constant amounts with ubiquitous distribution, neurofibromin protein, initially also ubiquitous, increases in total amount and becomes restricted to specific, largely neuronal, cell populations. We attempt to define neurofibromin's involvement in early neuron differentiation using mouse embryonic stem (ES) cells which contain targeted deletions of NF1. Examining the capacity for neuronal differentiation in ES cells containing two, one, or no functional copies of the NF1 gene, we observe that although neurofibromin is not required for this pathway of cell differentiation, differentiation is altered in its absence. We investigate two additional systems of ES cell differentiation to determine the neurofibromin requirement of each system. We find that while myeloid precursor cell differentiation is unaffected by lack of neurofibromin, embryoid body differentiation is altered in ES cells lacking neurofibromin. The three in vitro differentiation systems examined indicate that cells are capable of differentiation in the absence of neurofibromin, but this differentiation may be altered, depending on the cell type. | en_US |
dc.format.extent | 115 p. | en_US |
dc.subject | Biology, Molecular | en_US |
dc.title | Expression of and requirement for the NF1 gene product, neurofibromin, during cell differentiation in vivo and in vitro. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Cellular and Molecular Biology | en_US |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/104801/1/9610158.pdf | |
dc.description.filedescription | Description of 9610158.pdf : Restricted to UM users only. | en_US |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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