Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells
Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells
The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation.
McMurray, R.J.
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Wann, A.K.T.
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Thompson, C.L.
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Connelly, J.T.
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Knight, M.M.
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McMurray, R.J.
2e4cf997-4e4a-4daf-9d49-09b83abde8cf
Wann, A.K.T.
f1b0ea2f-dc8a-4588-a9d8-ae462ed0a993
Thompson, C.L.
f6a694f9-2c34-4baf-bd66-d8152432c277
Connelly, J.T.
b55269e7-36ab-44e4-be1d-623a8eadd5c7
Knight, M.M.
da926606-b5ef-48cb-8db8-8e4ddb85ed07
et al.
(2013)
Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells.
Scientific Reports, 3, [3545].
(doi:10.1038/SREP03545).
Abstract
The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation.
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srep03545
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Accepted/In Press date: 3 December 2013
e-pub ahead of print date: 18 December 2013
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Local EPrints ID: 488433
URI: http://eprints.soton.ac.uk/id/eprint/488433
ISSN: 2045-2322
PURE UUID: 170be12b-2541-4383-af5e-a0c3bd3399ee
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Date deposited: 22 Mar 2024 17:39
Last modified: 23 Mar 2024 03:11
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Author:
R.J. McMurray
Author:
A.K.T. Wann
Author:
C.L. Thompson
Author:
J.T. Connelly
Author:
M.M. Knight
Corporate Author: et al.
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