A new in vitro mouse oligodendrocyte precursor cell migration assay reveals a role for integrin-linked kinase in cell motility

[摘要] BackgroundThe decline of remyelination in chronic multiple sclerosis (MS) is in part attributed to inadequate oligodendrocyte precursor cell (OPC) migration, a process governed by the extracellular matrix (ECM). Elucidating the mechanisms underlying OPC migration is therefore an important step towards developing new therapeutic strategies to promote myelin repair. Many seminal OPC culture methods were established using rat-sourced cells, and these often need modification for use with mouse OPCs due to their sensitive nature. It is of interest to develop mouse OPC assays to leverage the abundant transgenic lines. To this end, we developed a new OPC migration method specifically suited for use with mouse-derived cells.ResultsTo validate its utility, we combined the new OPC migration assay with a conditional knockout approach to investigate the role of integrin-linked kinase (ILK) in OPC migration. ILK is a focal adhesion protein that stabilizes cellular adhesions to the extracellular matrix (ECM) by mediating a linkage between matrix-bound integrin receptors and the cytoskeleton. We identified ILK as a regulator of OPC migration on three permissive substrates. ILK loss produced an early, albeit transient, deficit in OPC migration on laminin matrix, while migration on fibronectin and polylysine was heavily reliant on ILK expression.ConclusionsInclusively, our work provides a new tool for studying mouse OPC migration and highlights the role of ILK in its regulation on ECM proteins relevant to MS.

[发布日期] 2016-02-01

[关键词] Mouse oligodendrocyte precursor cells;Migration;Integrin-linked kinase;Extracellular matrix;Laminin;Fibronectin;Polylysine