Induction of vertebrate heart development requires inhibition of canonical/<i>β</i>-catenin dependent Wnt signalling, activation of non-canonical/<i>β</i>-catenin independent Wnt signalling and transcription factor activation. Wnt/<i>β</i>-catenin signalling may also have a later regulatory role in cardiogenesis. The recent discovery of Wnt6 expression next to and within the developing heart during the relevant stages of cardiomyogenesis, combined with knockdown and over-expression data suggests that Wnt6 may have a role in the regulation of this process. Inhibition of canonical signalling leads to increased expression of cardiac associated transcription factors such as members of the Nkx2 and GATA family. These families are expressed in overlapping regions which specify the early heart field prior to the expression of the later cardiomyocyte-specific genes. This study demonstrates the ability of <i>β</i>-catenin to inhibit cardiogenesis during later developmental stages, before the cardiac mesoderm begins to differentiate into myocardium (heart muscle) and that the newly discovered Wnt6 exerts inhibition of cardiogenesis in a <i>β-</i>catenin<i> </i>dependent manner. This inhibition of cardiogenesis by <i>β-</i>catenin can occur in a cell-autonomous manner and is a result of direct inhibition of cardiac transcription factors of the GATA family. Over-expression of these pro-cardiogenic transcription factors GATA4 and GATA6 can restore the cardiomyogenic differentiation programme in embryos where it has previously been inhibited by <i>β</i>-catenin. In conclusion GATA factors are the relevant targets of Wnt/<i>β-</i>catenin signalling in the inhibition of normal cardiac development. The subsequent loss of cardiac gene expression observed is therefore a result of insufficient GATA expression and function.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:499647 |
| Date | January 2009 |
| Creators | Martin, Jennifer |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=25801 |
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