Characterisation of gamma-secretase role in the neurogenic-gliogenic shift in Ts1Cje mouse model of Down syndrome

Abstract

Event Abstract Back to Event Characterisation of gamma-secretase role in the neurogenic-gliogenic shift in Ts1Cje mouse model of Down syndrome Hadri H. Yusof1, 2, Han C. Lee1, 2, De M. Chau2, Pike S. Cheah1, 3 and King-Hwa Ling1, 2* 1 Genetics & Regenerative Medicine Research Centre (GRMRC), Neurobiology and Genetics Group, Malaysia 2 Universiti Putra Malaysia, Medical Genetics Unit, Department of Biomedical Sciences, Faculty of Medical and Health Sciences, Malaysia 3 Universiti Putra Malaysia, Department of Human Anatomy, Faculty of Medicine and Health Sciences, Malaysia Down syndrome (DS) is a disorder caused by an extra copy of chromosome 21 that increases expression of genes located on chromosome 21. This leads to a cascade of direct or indirect effect to the development of the foetal structure and subsequently alters their behaviour during the lifespan. DS is also characterised by the cardinal neurogenic-to-gliogenic shift during neurogenesis and cell-fate determination. To understand the underlying mechanism responsible for the shift, we utilised a mouse model for DS known as Ts1Cje, which also demonstrates the off-balance cellular shift in the brain. Notch-1 mediated signalling pathway is crucial for mammalian CNS development via maintenance of neural stem cell (progenitor) state and inhibition of neuronal commitment and promotion of glial cell fates. The components of gamma-secretase complex (PSEN, NCSTN, Aph-1b and PSENEN) are required for Notch protein cleavage and have link to neurogenesis and gliogenesis in the brain. We aim to profile the spatio-temporal gene expression patterns of gamma-secretase complexes and its primary downstream/upstream components and its effects in neurogenic-gliogenic shift using Ts1Cje mouse model. A total of 72 RNA samples from P1.5, P15, P30 and P84 cerebral cortices, cerebella and hippocampi from the brain of Ts1Cje and disomic mice were collected and converted into cDNA samples. These samples from different region were screened for gene expression study. The expression level of gamma-secretase complexes (PSEN1, NCSTN, Aph-1b, PSENEN) and also the Notch signalling proteins (Notch-1, Notch-2) were analysed using real-time quantitative PCR (qPCR). Preliminary results show no alterations in the expression level of the selected genes between the Ts1Cje and disomic mouse groups. This might be due to the heterogeneity of the cell population in the brain. Further expression study through in vitro neurosphere culture might give us a better insight of the real genetic expression. Acknowledgements The study was supported by Malaysian Ministry of Higher Education's Fundamental Research Grant Scheme awarded to P.-S. Cheah (FRGS/1/2015/SKK08/UPM/02/1) and Malaysian Ministry of Science, Technology and Innovation's Sciencefund grant awarded to K.-H. Ling (02-01-04-SF2336). Keywords: Down Syndrome, Gene Expression, gamma-secretase, Neurogenic, gliogenic Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Yusof HH, Lee HC, Chau DM, Cheah PS and Ling K (2016). Characterisation of gamma-secretase role in the neurogenic-gliogenic shift in Ts1Cje mouse model of Down syndrome. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00161 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Dr. King-Hwa Ling, Genetics & Regenerative Medicine Research Centre (GRMRC), Neurobiology and Genetics Group, UPM Serdang, Selangor, Malaysia, lkh@upm.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Hadri H Yusof Han C Lee De M Chau Pike S Cheah King-Hwa Ling Google Hadri H Yusof Han C Lee De M Chau Pike S Cheah King-Hwa Ling Google Scholar Hadri H Yusof Han C Lee De M Chau Pike S Cheah King-Hwa Ling PubMed Hadri H Yusof Han C Lee De M Chau Pike S Cheah King-Hwa Ling Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.