title: Substrate topography determines neuronal polarization and growth in vitro.
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.
authors.affiliation: Life Science Technologies, Imec, Leuven, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Micholt
authors.forename: Annette
authors.initials: A
authors.lastname: Gärtner
authors.forename: Dimiter
authors.initials: D
authors.lastname: Prodanov
authors.forename: Dries
authors.initials: D
authors.lastname: Braeken
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Dotti
authors.forename: Carmen
authors.initials: C
authors.lastname: Bartic
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism; D051379:Mice; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D015820:Cadherins; D014443:Tyrosine