Han-Chung Lee1,2, Hadri Hadi Md Yusof1,2, Melody Pui-Yee Leong1,2, Shahidee Zainal Abidin1,2, Eryse Amira Seth1,3, Chelsee A Hewitt4, Sharmili Vidyadaran1,5, Norshariza Nordin1,2, Hamish S Scott6,7,8,9, Pike-See Cheah1,3, King-Hwa Ling1,2. 1. a Genetics and Regenerative Medicine Research Centre (GRMRC), Faculty of Medicine and Health Sciences , Universiti Putra Malaysia , Selangor , Malaysia. 2. b Department of Biomedical Science, Faculty of Medicine and Health Sciences , Universiti Putra Malaysia , Selangor , Malaysia. 3. c Department of Human Anatomy, Faculty of Medicine and Health Sciences , Universiti Putra Malaysia , Serdang , Selangor , Malaysia. 4. e Department of Pathology , The Peter MacCallum Cancer Centre , East Melbourne , Victoria , Australia. 5. d Department of Pathology, Immunology Unit, Faculty of Medicine and Health Sciences , Universiti Putra Malaysia , Serdang , Selangor , Malaysia. 6. f Department of Genetics and Molecular Pathology, Centre for Cancer Biology , An alliance between SA Pathology and the University of South Australia, SA Pathology , Adelaide , Australia. 7. g School of Pharmacy and Medical Science , University of South Australia , Adelaide , Australia. 8. h School of Medicine, School of Biological Sciences , University of Adelaide , Adelaide , South Australia. 9. i Centre for Cancer Biology, SA Pathology , Australian Cancer Research Foundation Genomics Facility , Adelaide , Australia.
Abstract
Aims: The JAK-STAT signalling pathway is one of the key regulators of pro-gliogenesis process during brain development. Down syndrome (DS) individuals, as well as DS mouse models, exhibit an increased number of astrocytes, suggesting an imbalance of neurogenic-to-gliogenic shift attributed to dysregulated JAK-STAT signalling pathway. The gene and protein expression profiles of JAK-STAT pathway members have not been characterised in the DS models. Therefore, we aimed to profile the expression of Jak1, Jak2, Stat1, Stat3 and Stat6 at different stages of brain development in the Ts1Cje mouse model of DS. Methods: Whole brain samples from Ts1Cje and wild-type mice at embryonic day (E)10.5, E15, postnatal day (P)1.5; and embryonic cortex-derived neurospheres were collected for gene and protein expression analysis. Gene expression profiles of three brain regions (cerebral cortex, cerebellum and hippocampus) from Ts1Cje and wild-type mice across four time-points (P1.5, P15, P30 and P84) were also analysed. Results: In the developing mouse brain, none of the Jak/Stat genes were differentially expressed in the Ts1Cje model compared to wild-type mice. However, Western blot analyses indicated that phosphorylated (p)-Jak2, p-Stat3 and p-Stat6 were downregulated in the Ts1Cje model. During the postnatal brain development, Jak/Stat genes showed complex expression patterns, as most of the members were downregulated at different selected time-points. Notably, embryonic cortex-derived neurospheres from Ts1Cje mouse brain expressed lower Stat3 and Stat6 protein compared to the wild-type group. Conclusion: The comprehensive expression profiling of Jak/Stat candidates provides insights on the potential role of the JAK-STAT signalling pathway during abnormal development of the Ts1Cje mouse brains.
Aims: The JAK-STAT signalling pathway is one of the key regulators of pro-gliogenesis process during brain development. Down syndrome (DS) individuals, as well as DS mouse models, exhibit an increased number of astrocytes, suggesting an imbalance of neurogenic-to-gliogenic shift attributed to dysregulated JAK-STAT signalling pathway. The gene and protein expression profiles of JAK-STAT pathway members have not been characterised in the DS models. Therefore, we aimed to profile the expression of Jak1, Jak2, Stat1, Stat3 and Stat6 at different stages of brain development in the Ts1Cjemouse model of DS. Methods: Whole brain samples from Ts1Cje and wild-type mice at embryonic day (E)10.5, E15, postnatal day (P)1.5; and embryonic cortex-derived neurospheres were collected for gene and protein expression analysis. Gene expression profiles of three brain regions (cerebral cortex, cerebellum and hippocampus) from Ts1Cje and wild-type mice across four time-points (P1.5, P15, P30 and P84) were also analysed. Results: In the developing mouse brain, none of the Jak/Stat genes were differentially expressed in the Ts1Cje model compared to wild-type mice. However, Western blot analyses indicated that phosphorylated (p)-Jak2, p-Stat3 and p-Stat6 were downregulated in the Ts1Cje model. During the postnatal brain development, Jak/Stat genes showed complex expression patterns, as most of the members were downregulated at different selected time-points. Notably, embryonic cortex-derived neurospheres from Ts1Cjemouse brain expressed lower Stat3 and Stat6 protein compared to the wild-type group. Conclusion: The comprehensive expression profiling of Jak/Stat candidates provides insights on the potential role of the JAK-STAT signalling pathway during abnormal development of the Ts1Cjemouse brains.