Student Theses and Dissertations

Wei-Ming Yu

Date of Award

2007

Document Type

Thesis

RU Laboratory

Strickland Laboratory

Keywords

Schwann cells, laminin y1 gene, nerve development

Abstract

To investigate the function of laminins in peripheral nerve development, the laminin γ1 gene was specifically disrupted in Schwann cells. Disruption of laminin γ1 gene expression resulted in depletion of all other laminin chains known to be expressed in Schwann cells. Schwann cells lacking laminins fail to differentiate to myelinating and non-myelinating Schwann cells and do not extend processes required for initiating axonal sorting and mediating axon-Schwann cell interactions. These cells also fail to down-regulate Oct-6 and they arrest at the premyelinating stage. Impaired axon-Schwann cell interactions prevent phosphorylation of β-neuregulin-1 receptors, which results in decreased cell proliferation. Postnatally, laminin-null Schwann cells exhibit reduced phosphatidylinositol 3-kinase activity and activation of caspase cascades, leading to apoptosis. Injection of a laminin peptide into mutant sciatic nerves partially restores PI 3-kinase activity and reduces apoptotic signals. In a Schwann cell/dorsal root ganglion co-culture system, disruption of laminins impairs podia formation as well as the elongation of Schwann cells. These results demonstrate that: 1) laminins initiate axonal sorting and mediate axon-Schwann cell interactions required for Schwann cell proliferation and differentiation; 2) laminins provide a PI 3-kinase/Akt-mediated Schwann cell survival signal.

Comments

A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

Permanent URL

http://hdl.handle.net/10209/141

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