1. Exploring the function of glutamine fructose-6-phosphate transaminase (GFPT2) in embryonic development
- Author
-
Dunwoodie, Sally, Victor Chang Cardiac Research Institute, UNSW, Dawes, Ian, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW, Woolford, Michelle, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW, Dunwoodie, Sally, Victor Chang Cardiac Research Institute, UNSW, Dawes, Ian, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW, and Woolford, Michelle, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW
- Abstract
The aim of this thesis was to identify genes expressed in the heart during early mouse development, and to determine their function in mouse heart development. Microarray technology was used to expression profile the progenitor tissue of the heart, the mesoderm. A subset of genes identified as enriched in the progenitor tissues of the heart with no or little published expression data were selected for examination by whole mount RNA in situ hybridisation in 7.5 dpc, 8.5 dpc and 9.5 dpc mouse embryos. None of the genes examined were expressed in a restricted manner in the developing heart.In another screen being undertaken in our laboratory, Glutamine fructose-6-phosphate transaminase 2 (Gfpt2) was identified as being expressed in a restricted manner in the developing heart at 9.5 dpc. Gfpt is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP). This pathway accounts for 1-3 % of glucose metabolism in the cell, and converts fructose-6-phosphate to uridine-N-acetylglucoasmine (UDP-GlcNAc), which is responsible for the majority of glycosylation in the cell. In the mouse, two separate and differentially regulated genes can each encode for Gfpt, Gfpt1 and Gfpt2. Prior to this study, Gfpt expression had not been examined in mouse development.Gfpt1 and Gfpt2 are differentially expressed. Gfpt2 expression was detected in the foregut endoderm at 8.5 dpc, and in the myocardium underlying the cardiac cushions at 9.5 dpc. Gfpt2 was also detected in the pre-somitic mesoderm at 9.5dpc and latter stages, branchial arches and forebrain of the embryo. Gfpt1 expression was not detected in the mouse embryo at these stages, but was detected in the placenta from 9.5 dpc.The expression pattern of Gfpt2 in the developing mouse and the known function of Gfpt2 in the HBP led to the hypothesis that Gfpt2 expression correlated to an increased requirement for UDP-GlcNAc in the tissues in which it is expressed. To investigate this, mice carrying gene traps within the enzymatic
- Published
- 2012