Prostaglandin E2 alters Wnt-dependent migration and proliferation in neuroectodermal stem cells: implications for autism spectrum disorders

Cell Communication and Signaling

Research

Eizaaz Ahmad¹  Hongyan Li²  Christine T Wong³  Dorota A Crawford⁴ 

[1] Department of Biology, Faculty of Health, York University, 4700 Keele Street, M3J 1P3, Toronto, Ontario, Canada;School of Kinesiology and Health Science, York University, 4700 Keele Street, M3J 1P3, Toronto, Ontario, Canada;School of Kinesiology and Health Science, York University, 4700 Keele Street, M3J 1P3, Toronto, Ontario, Canada;Neuroscience Graduate Diploma Program, York University, 4700 Keele Street, M3J 1P3, Toronto, Ontario, Canada;School of Kinesiology and Health Science, York University, 4700 Keele Street, M3J 1P3, Toronto, Ontario, Canada;Neuroscience Graduate Diploma Program, York University, 4700 Keele Street, M3J 1P3, Toronto, Ontario, Canada;Department of Biology, Faculty of Health, York University, 4700 Keele Street, M3J 1P3, Toronto, Ontario, Canada;

关键词: Prostaglandin E2;    Wnt signalling;    Neuroectodermal stem cells;    Cell motility;    Proliferation;    Autism;   

DOI  :  10.1186/1478-811X-12-19

 received in 2013-09-13, accepted in 2014-03-13,  发布年份 2014

来源: Springer

【 摘 要 】

Prostaglandin E2 (PGE2) is a natural lipid-derived molecule that is involved in important physiological functions. Abnormal PGE2 signalling has been associated with pathologies of the nervous system. Previous studies provide evidence for the interaction of PGE2 and canonical Wnt signalling pathways in non-neuronal cells. Since the Wnt pathway is crucial in the development and organization of the brain, the main goal of this study is to determine whether collaboration between these pathways exists in neuronal cell types. We report that PGE2 interacts with canonical Wnt signalling through PKA and PI-3K in neuroectodermal (NE-4C) stem cells. We used time-lapse microscopy to determine that PGE2 increases the final distance from origin, path length travelled, and the average speed of migration in Wnt-activated cells. Furthermore, PGE2 alters distinct cellular phenotypes that are characteristic of Wnt-induced NE-4C cells, which corresponds to the modified splitting behaviour of the cells. We also found that in Wnt-induced cells the level of β-catenin protein was increased and the expression levels of Wnt-target genes (Ctnnb1, Ptgs2, Ccnd1, Mmp9) was significantly upregulated in response to PGE2 treatment. This confirms that PGE2 activated the canonical Wnt signalling pathway. Furthermore, the upregulated genes have been previously associated with ASD. Our findings show, for the first time, evidence for cross-talk between PGE2 and Wnt signalling in neuronal cells, where PKA and PI-3K might act as mediators between the two pathways. Given the importance of PGE2 and Wnt signalling in prenatal development of the nervous system, our study provides insight into how interaction between these two pathways may influence neurodevelopment.

【 授权许可】

Unknown   
© Wong et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.