The effect of alternative neuronal differentiation pathways on PC12 cell adhesion and neurite alignment to nanogratings

Ferrari, Aldo; Faraci, Paolo; Cecchini, Marco; Beltram, Fabio (2010). The effect of alternative neuronal differentiation pathways on PC12 cell adhesion and neurite alignment to nanogratings. Biomaterials, 31(9), pp. 2565-73. Oxford: Elsevier 10.1016/j.biomaterials.2009.12.010

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During development and regeneration of the mammalian nervous system, directional signals guide differentiating neurons toward their targets. Soluble neurotrophic molecules encode for preferential direction over long distances while the local topography is read by cells in a process requiring the establishment of focal adhesions. The mutual interaction between overlapping molecular and topographical signals introduces an additional level of control to this picture. The role of the substrate topography was demonstrated exploiting nanotechnologies to generate biomimetic scaffolds that control both the polarity of differentiating neurons and the alignment of their neurites. Here PC12 cells contacting nanogratings made of copolymer 2-norbornene ethylene (COC), were alternatively stimulated with Nerve Growth Factor, Forskolin, and 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cyclic (8CPT-2Me-cAMP) or with a combination of them. Topographical guidance was differently modulated by the alternative stimulation protocols tested. Forskolin stimulation reduced the efficiency of neurite alignment to the nanogratings. This effect was linked to the inhibition of focal adhesion maturation. Modulation of neurite alignment and focal adhesion maturation upon Forskolin stimulation depended on the activation of the MEK/ERK signaling but were PkA independent. Altogether, our results demonstrate that topographical guidance in PC12 cells is modulated by the activation of alternative neuronal differentiation pathways.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Cecchini, Marco Giovanni

ISSN:

0142-9612

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:10

Last Modified:

04 May 2014 23:05

Publisher DOI:

10.1016/j.biomaterials.2009.12.010

PubMed ID:

20035995

Web of Science ID:

000275348800014

URI:

https://boris.unibe.ch/id/eprint/1255 (FactScience: 202409)

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