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THE ROLE OF SCHWANN CELLS IN THE FORMATION OF THE
NEUROMUSCULAR JUNCTION
by
Zhihua Feng
A Dissertation presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
December 2007
Copyright 2007 Zhihua Feng
Object Description
| Title | The role of Schwann cells in the development of the neuromuscular junction |
| Author | Feng, Zhihua |
| Author email | zfeng@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2007-10-19 |
| Date submitted | 2007 |
| Restricted until | Restricted until 16 Nov. 2009. |
| Date published | 2009-11-16 |
| Advisor (committee chair) | Ko, Chien-Ping |
| Advisor (committee member) |
Byerly, Lou Butler, Samantha Herrera, Albert Ying, Shao-Yao |
| Abstract | Recent findings have demonstrated that synapse-associated glial cells are an integral and essential component of the tripartite synapse. Glial cells at the vertebrate neuromuscular junction (NMJ), perisynaptic Schwann cells (PSCs), also actively participate in the formation, function, maintenance and repair of the NMJ. However, the molecular mechanism of PSC-NMJ interaction is largely unknown. To explore how PSCs promote synapse formation, in this dissertation we examined whether and how Schwann cell-derived molecules promote synaptogenesis in Xenopus nerve-muscle co-cultures. We have shown that when Xenopus spinal neurons were stimulated with a mixture of neurotrophins plus cAMP elevation, neuronal survival and neurite outgrowth were greatly enhanced. However, synaptogenesis, as demonstrated by the clustering of acetylcholine receptors (AChRs) at nerve-muscle contacts, was largely reduced. Agrin deposition along growing neurites was also inhibited, which may contribute to the decreased synapse formation. Additionally, trophic stimulus also inhibited both the synthesis of agrin protein and mRNA via directly acting on pre-synaptic neurons. Thus, trophic stimulus promotes neurons in the growth state.; We have also demonstrated that both agrin synthesis and agrin deposition were restored when Schwann cell-conditioned medium (SC-CM) was added to co-cultures with trophic stimulus. Furthermore, the synaptogenic ability of neurons was also restored by molecules derived from Schwann cells. Schwann cells therefore help switch neurons from their growth state to the synaptogenesis state. We have illustrated that Schwann cell-derived transforming growth factor (TGF)-beta1 elicits a similar effect as SC-CM in promoting synapse formation, and is likely mediating the synaptogenic effect of Schwann cells. TGF-beta1 also up-regulates neuronal agrin expression, which may explain the enhanced synapse formation in TGF-beta1 treated co-cultures. These results suggest that Schwann cells release TGF-beta1, which promotes synapse formation at the developing NMJ. Our findings support the emerging concept that glial cells are active players at the chemical synapse, and provide a potential mechanism by which Schwann cells promote synapse formation during development. |
| Keyword | Schwann cells |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m930 |
| Rights | Feng, Zhihua |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Feng-20071116 |
| Archival file | uscthesesreloadpub_Volume62/etd-Feng-20071116.pdf |
Description
| Title | Page 1 |
| Full text | THE ROLE OF SCHWANN CELLS IN THE FORMATION OF THE NEUROMUSCULAR JUNCTION by Zhihua Feng A Dissertation presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) December 2007 Copyright 2007 Zhihua Feng |
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