Date of Award
Schwann cells, laminin y1 gene, nerve development
To investigate the function of laminins in peripheral nerve development, the laminin Î³1 gene was specifically disrupted in Schwann cells. Disruption of laminin Î³1 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 Î²-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.
Yu, Wei-Ming, "Role of Laminins in the Development of the Peripheral Nervous System" (2007). Student Theses and Dissertations. 30.