Abstract / Description of output
Without Focal Adhesion Kinase (FAK), developing murine Schwann cells (SCs) proliferate poorly, sort axons inefficiently, and cannot myelinate peripheral nerves. Here we show that FAK is required for the development of SCs when their basal lamina (BL) is fragmentary, but not when it is mature in vivo. Mutant SCs fail to spread on fragmentary BL during development in vivo, and this is phenocopied by SCs lacking functional FAK on low laminin (LN) in vitro. Furthermore, SCs without functional FAK initiate differentiation prematurely, both in vivo and in vitro. In contrast to their behavior on high levels of LN, SCs lacking functional FAK grown on low LN display reduced spreading, proliferation, and indicators of contractility (i.e., stress fibers, arcs, and focal adhesions) and are primed to differentiate. Growth of SCs lacking functional FAK on increasing LN concentrations in vitro revealed that differentiation is not regulated by G1 arrest but rather by cell spreading and the level of contractile actomyosin. The importance of FAK as a critical regulator of the specific response of developing SCs to fragmentary BL was supported by the ability of adult FAK mutant SCs to remyelinate demyelinated adult nerves on mature BL in vivo. We conclude that FAK promotes the spreading and actomyosin contractility of immature SCs on fragmentary BL, thus maintaining their proliferation, and preventing differentiation until they reach high density, thereby promoting radial sorting. Hence, FAK has a critical role in the response of SCs to limiting BL by promoting proliferation and preventing premature SC differentiation.
Original language | English |
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Pages (from-to) | 13422-13434 |
Number of pages | 13 |
Journal | Journal of Neuroscience |
Volume | 34 |
Issue number | 40 |
DOIs | |
Publication status | Published - 1 Oct 2014 |
Keywords / Materials (for Non-textual outputs)
- basal lamina
- FAK
- myelination
- Schwann cell
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Peter Brophy
- Centre for Discovery Brain Sciences
- Edinburgh Neuroscience
- Deanery of Biomedical Sciences - UoE Retired Staff
Person: Academic: Research Active , Affiliated Independent Researcher