TitleMolecular mechanisms regulating Schwann cell development and injury response in the PNS
NameYang, Po-Lung (author), Bonder, Edward (chair), Kim, Haesun (internal member), Friedman, Wilma (internal member), Einheber, Steven (outside member), Rutgers University, Graduate School - Newark,
DescriptionThe work within examined different aspects of the Schwann cell (SC) development and injury response: the initial demyelination, de-differentiation, and the proliferation that follows. Previous studies have shown that demyelination in the PNS often results from hijacking of these pathways, leading to SC demyelination and proliferation. Therefore, understanding of the mechanism is important as it provides insight into developing therapeutic strategies for various demyelinating neuropathies. The work described in the first chapter focuses on the mechanism of demyelination and identified p38 MAPK as an important regulator of SC demyelination. Using both in vivo and in vitro methods for nerve injury, I showed that p38 MAPK inhibition strongly reduced demyelination whereas its ectopic activation resulted in spontaneous demyelination. After SCs de-differentiate and demyelinate, the distal SCs become highly proliferative, participating in the injury response to promote functional recovery. The proliferation of SCs is thought to be an important component of the injury repair processes. Further understanding of these processes may help in promoting functional recovery after nerve injury. The second part of the thesis examined the role of SC proliferation that occurs during this period. Using a transgenic animal model in which SCs do not proliferate after injury, I showed that SC proliferation is not required for functional recovery, but rather the excess SCs generated during this proliferative period are removed by apoptosis. Finally, in the third chapter the function of a transcription factor Dlx1 during SC development was examined. Results showed that Dlx1 specifically regulates development of the non-myelinating SC lineage. In the absence of Dlx1, radial sorting of the axons by non-myelinating SCs is impaired; axons in the Remak bundles remain clustered and unsegregated. Biochemical analysis showed alteration in the activation state of several regulators of cytoskeletal dynamics and cell morphology. Correspondingly, Dlx1-deficient SCs exhibit defects in radial lamellae formation, which may account for the axon sorting defect observed in vivo. Overall, these studies further our understanding of SC biology and provide additional insights into molecular regulators of SC development and injury response.
NoteIncludes bibliographical references
Noteby Po-Lung Yang
CollectionGraduate School - Newark Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.