The Functional Characterization of Alpha-V Integrins and the Mechanotransduction Signaling in Schwann Cells
Catignas Markham, Kathleen
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In the developing peripheral nerve, neurons and Schwann cells (SC) associate intimately, and by mechanisms still poorly understood, they communicate reciprocally to ensure that neurons are myelinated, supported, and protected throughout the life of the organism. Poor SC-neuron connections can manifest as neuropathy; hence it is crucial to understand the basis of their communication. Early on, Schwann cells mature and differentiate to become fully functional, myelinating cells, with all phases of their development completely dependent on axon contact. The mechanisms behind how axons signal Schwann cells to differentiate are not well-defined, but cell-cell contact/adhesion between these two cell types could facilitate such a signaling exchange. This thesis work aims to understand how SC-axon communication is facilitated through cell-adhesion molecules such as integrins to achieve myelination. The goal is to determine the role of a subset of integrins, the RGD-binding αV integrins, found to be expressed by axon-related Schwann cells during development. In vitro perturbation of these αV integrins result in stunted Schwann cells that are delayed in their elongation on axons, suggesting that Schwann cells utilize αV integrins to initiate elongation on axons. Selective ablation of SC αV in vivo produce normal animals, suggesting that another integrin such as α5 may compensate for the absence of αV. Double conditional deletion of αV and α5 integrins, however, also produce normal animals. These suggest that a) both integrins are dispensable for development, b) other molecules may compensate or functionally overlap, or c) αV/α5 may instead function in a stressed context such as nerve injury. This work nevertheless identifies SC αV integrins as a potential mediator of SC-axon interactions. It sheds light on the elusive stages of myelination and points to a potential mechanism that may drive contact/adhesion and communication between Schwann cells and neurons.