Characterisation of gamma-secretase role in the neurogenic-gliogenic shift in Ts1Cje mouse model of Down syndrome
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1
Genetics & Regenerative Medicine Research Centre (GRMRC), Neurobiology and Genetics Group, Malaysia
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2
Universiti Putra Malaysia, Medical Genetics Unit, Department of Biomedical Sciences, Faculty of Medical and Health Sciences, Malaysia
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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
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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