Dissecting Gene Expression Networks in Mammalian Organogenesis (MORGEN)
Using the mouse as our model organism, we are identifying transcriptional networks of genes necessary for the development of the heart, lung, and pancreas.
|Project Leaders||Marco Marra , Pamela Hoodless|
|Project Co-Investigators||Aly Karsan , Cheryl Helgason , Steven Jones , Sid Katz, Ed Levy|
Genome Sciences Centre
BC Cancer Research Centre
University of British Columbia
Genome British Columbia
Heart and Stroke Foundation of BC/Yukon
British Columbia Knowledge Development Fund
Juvenile Diabetes Research Foundation
BC Cancer Foundation
Michael Smith Foundation for Health Research
|Project Web site||http://www.mouseatlas.org/morgen|
The development of a creature from a single cell to a multi-cellular organism with each tissue and organ having a distinct architecture and function is truly remarkable. Cells must co-operate and communicate with one another so they divide, migrate, form connections, die, and change their identity in complex and co-ordinated patterns. Understanding how regulation of gene expression controls the development of tissues and organs in the embryo has far reaching implications for medical therapies, ranging from the problems associated with repairing congenital defects to new promising technologies such as stem cell therapies and tissue engineering. To accomplish these goals, it is necessary to fully understand how organs form. The MORGEN project aims to investigate the gene networks that regulate this process.
In the MORGEN project we have chosen to focus on the development of three organs in the mouse embryo, the heart, pancreas and liver. In particular, we will focus on tissues in the heart involved in valve formation and septation of the chambers, in the pancreas on the formation of islet cells, and in the liver on hepatocytes. Gene expression profiles in the chosen tissues at different times of development are being generated using Serial Analysis of Gene Expression (SAGE). To understand how gene expression is controlled, the critical transcription factors that regulate these genes are being investigated. In addition, we are developing techniques to identify genome-wide binding patterns of these specific transcriptional factors using chromatin immunoprecipitation coupled with sequencing.
The MORGEN project will provide a complete, permanent, and accurate picture of mouse gene expression in the heart (atrioventricular canal and outflow tract), pancreas, and liver; new techniques to understand the interplay of proteins governing the expression of genes key to the development of these organ systems; and the identification of the “master regulatory switches” that control development of the tissues.
Publications by the MORGEN Team:
- Hoffman BG, Robertson G, Zavaglia B, Beach M, Cullum R, Lee S, Soukhatcheva G, Li L, Wederell ED, Thiessen N, Bilenky M, Cezard T, Tam A, Kamoh B, Birol I, Dai D, Zhao Y, Hirst M, Verchere CB, Helgason CD, Marra MA, Jones SJ, Hoodless PA. 2010. Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver.. Genome Res. 2010 Jun 15. [Epub ahead of print]
- Vrljicak PJ, Chang AC, Morozova O, Wederell ED, Niessen K, Marra MA, Karsan A, Hoodless PA. 2009. Genomic Analysis Distinguishes Phases of Early Development of the Mouse Atrio-Ventricular Canal. Physiol Genomics. [Epub ahead of print Dec 1]
- Robertson AG, Bilenky M, Tam A, Zhao Y, Zeng T, Thiessen N, Cezard T, Fejes AP, Wederell ED, Cullum R, Euskirchen G, Krzywinski M, Birol I, Snyder M, Hoodless PA, Hirst M, Marra MA, Jones SJ. 2008. Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding. Genome Res. 18(12):1906-17. Epub 2008 Sep 11.
- Wederell ED, Bilenky M, Cullum R, Thiessen N, Dagpinar M, Delaney A, Varhol R, Zhao Y, Zeng T, Bernier B, Ingham M, Hirst M, Robertson G, Marra MA, Jones S, Hoodless PA. 2008. Global analysis of in vivo Foxa2-binding sites in mouse adult liver using massively parallel sequencing. Nucleic Acids Res. 36(14):4549-64. Epub 2008 Jul 8.
- Hoffman BG, Zavaglia B, Witzsche J, Ruiz de Algara T, Beach M, Hoodless PA, Jones SJ, Marra MA, Helgason CD. 2008. Identification of transcripts with enriched expression in the developing and adult pancreas. Genome Biol. 9(6):R99. Epub 2008 Jun 14.
- Hou J, Charters AM, Lee SC, Zhao Y, Wu MK, Jones SJ, Marra MA, Hoodless PA. 2007. A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE). BMC Dev Biol. 7:92.
- Khattra J, Delaney AD, Zhao Y, Siddiqui A, Asano J, McDonald H, Pandoh P, Dhalla N, Prabhu AL, Ma K, Lee S, Ally A, Tam A, Sa D, Rogers S, Charest D, Stott J, Zuyderduyn S, Varhol R, Eaves C, Jones S, Holt R, Hirst M, Hoodless PA, Marra MA. 2007. Large-scale production of SAGE libraries from microdissected tissues, flow-sorted cells, and cell lines. Genome Res. 17(1):108-16. Epub 2006 Nov 29.
- Siddiqui AS, Khattra J, Delaney AD, Zhao Y, Astell C, Asano J, Babakaiff R, Barber S, Beland J, Bohacec S, Brown-John M, Chand S, Charest D, Charters AM, Cullum R, Dhalla N, Featherstone R, Gerhard DS, Hoffman B, Holt RA, Hou J, Kuo BY, Lee LL, Lee S, Leung D, Ma K, Matsuo C, Mayo M, McDonald H, Prabhu AL, Pandoh P, Riggins GJ, de Algara TR, Rupert JL, Smailus D, Stott J, Tsai M, Varhol R, Vrljicak P, Wong D, Wu MK, Xie YY, Yang G, Zhang I, Hirst M, Jones SJ, Helgason CD, Simpson EM, Hoodless PA, Marra MA. 2005. A mouse atlas of gene expression: large-scale digital gene-expression profiles from precisely defined developing C57BL/6J mouse tissues and cells. Proc Natl Acad Sci U S A. 102(51):18485-90. Epub 2005 Dec 13
For all project related inquires please contact us.
Joanne Johnson, Project Manager
Genome Sciences Centre, BC Cancer Agency
Phone: 604-675-8000 x 7901