Substrate Topography Determines Neuronal Polarization and Growth In Vitro
Open Access
- 13 June 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (6), e66170
- https://doi.org/10.1371/journal.pone.0066170
Abstract
The establishment of neuronal connectivity depends on the correct initial polarization of the young neurons. In vivo, developing neurons sense a multitude of inputs and a great number of molecules are described that affect their outgrowth. In vitro, many studies have shown the possibility to influence neuronal morphology and growth by biophysical, i.e. topographic, signaling. In this work we have taken this approach one step further and investigated the impact of substrate topography in the very early differentiation stages of developing neurons, i.e. when the cell is still at the round stage and when the first neurite is forming. For this purpose we fabricated micron sized pillar structures with highly reproducible feature sizes, and analyzed neurons on the interface of flat and topographic surfaces. We found that topographic signaling was able to attract the polarization markers of mouse embryonic neurons -N-cadherin, Golgi-centrosome complex and the first bud were oriented towards topographic stimuli. Consecutively, the axon was also preferentially extending along the pillars. These events seemed to occur regardless of pillar dimensions in the range we examined. However, we found differences in neurite length that depended on pillar dimensions. This study is one of the first to describe in detail the very early response of hippocampal neurons to topographic stimuli.Keywords
This publication has 51 references indexed in Scilit:
- N-cadherin specifies first asymmetry in developing neuronsThe EMBO Journal, 2012
- Biophysics of substrate interaction: Influence on neural motility, differentiation, and repairDevelopmental Neurobiology, 2011
- Topography, Cell Response, and Nerve RegenerationAnnual Review of Biomedical Engineering, 2010
- Myosin II activity regulates vinculin recruitment to focal adhesions through FAK-mediated paxillin phosphorylationThe Journal of cell biology, 2010
- Mechanosensitivity of fibroblast cell shape and movement to anisotropic substratum topography gradientsBiomaterials, 2009
- Myosin II Motors and F-Actin Dynamics Drive the Coordinated Movement of the Centrosome and Soma during CNS Glial-Guided Neuronal MigrationNeuron, 2009
- Textural guidance cues for controlling process outgrowth of mammalian neuronsLab on a Chip, 2008
- New insights into the molecular mechanisms specifying neuronal polarity in vivoCurrent Opinion in Neurobiology, 2008
- Focal adhesion kinase: in command and control of cell motilityNature Reviews Molecular Cell Biology, 2005
- FAK–Src signalling through paxillin, ERK and MLCK regulates adhesion disassemblyNature, 2004