Expression of dominant-negative and chimeric subunits reveals an essential role for β1 integrin during myelination

João B. Relvas, Anna Setzu, Wia Baron, Philip C. Buttery, Susan E. LaFlamme, Robin J.M. Franklin, Charles Ffrench-Constant

Research output: Contribution to journalArticlepeer-review

92 Citations (Scopus)


Myelination represents a remarkable example of cell specialization and cell-cell interaction in development. During this process, axons are wrapped by concentric layers of cell membrane derived either from central nervous system (CNS) oligodendrocytes or peripheral nervous system Schwann cells. In the CNS, oligodendrocytes elaborate a membranous extension with an area of more than 1000 times that of the cell body [1]. The mechanisms regulating this change in cell shape remain poorly understood. Signaling mechanisms regulated by cell surface adhesion receptors of the integrin family represent likely candidates. Integrins link the extracellular environment of the cell with both intracellular signaling molecules and the cytoskeleton and have been shown to regulate the activity of GTPases implicated in the control of cell shape [2]. Our previous work has established that oligodendrocytes and their precursors express a limited repertoire of integrins [3, 4]. One of these, the α6β1 laminin receptor, can interact with laminin-2 substrates to enhance oligodendrocyte myelin membrane formation in cell culture [5]. However, these experiments do not address the important question of integrin function during myelination in vivo, nor do they define the respective roles of the α and β subunits in the signaling pathways involved. Here, we use a dominant-negative approach to provide, for the first time, evidence that β1 integrin function is required for myelination in vivo and use chimeric integrins to dissect apart the roles of the extracellular and cytoplasmic domains of the α6 subunit in the signaling pathways of myelination.

Original languageEnglish
Pages (from-to)1039-1043
Number of pages5
JournalCurrent Biology
Issue number13
Publication statusPublished - 10 Jul 2001

Cite this