dc.creator | Tahaei, Seyedmohammad Ebrahim | |
dc.date.accessioned | 2020-08-21T20:57:04Z | |
dc.date.available | 2020-01-22 | |
dc.date.issued | 2018-01-22 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-01222018-164000 | |
dc.identifier.uri | http://hdl.handle.net/1803/10471 | |
dc.description.abstract | Neurofibromatosis type 1 results from mutations in NF1, a gene that encodes Neurofibromin. This common genetic condition is associated with tibial pseudarthrosis (PA), whose etiology is unknown but thought to involve defective bone-repairing osteoprogenitors. The main objective of my thesis was to delineate the causal determinants of the poor osteogenic potential of Nf1-/- osteoprogenitors. I showed that increased Epiregulin and TGFb1 expression does not contribute
to the reduced osteogenic differentiation of Nf1-/- osteoprogenitors, and contrary to all expectations, that this phenotype is likely independent from MAPK/ERK constitutive signaling. Using a RNA-Seq approach, I identified changes in pro-inflammatory and extracellular matrix gene signatures as putative determinants of the impaired differentiation of Nf1-/- osteoprogenitors. Finally, I obtained preliminary data pointing to inhibition of RUNX2 activity upon loss of Nf1 function. These results suggest unexpected interactions between Neurofibromin and proximal cell signaling/adhesion components that impact not one but multiple downstream signaling pathways. | |
dc.format.mimetype | application/pdf | |
dc.subject | RNA-Seq | |
dc.subject | Neurofibromatosis type 1 | |
dc.subject | Bone marrow stroll cells | |
dc.subject | Differentiation | |
dc.subject | MAPK signaling | |
dc.subject | Epiregulin | |
dc.title | Molecular Bases of the Reduced Osteogenic Differentiation Potential in Nf1 Deficient
Osteoprogenitors | |
dc.type | dissertation | |
dc.contributor.committeeMember | Florent Elefteriou | |
dc.contributor.committeeMember | Alan Brash | |
dc.contributor.committeeMember | Ana Carneiro | |
dc.contributor.committeeMember | Jeffrey Davidson | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Pharmacology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2020-01-22 | |
local.embargo.lift | 2020-01-22 | |
dc.contributor.committeeChair | Joey Barnett | |