Proceedings of The Physiological Society

Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, PC214

Poster Communications

Using Drosophila to study functional relevance of conserved heart genes

J. Catterson1, P. O. Bagnaninchi2, A. J. Harmar1, M. M. Heck1, P. S. Hartley1

1. Centre for Cardiovascular Science, University Of Edinburgh, Edinburgh, United Kingdom. 2. MRC Centre for Regenerative Medicine, University Of Edinburgh, Edinburgh, United Kingdom.

Drosophila melanogaster is increasingly utilised as a model of heart development and function due to its unparalleled genetic toolbox and fast experimental turnaround. We utilised the Fly Atlas database (the fruit fly gene expression atlas) to identify genes enriched in the adult fly heart that have high sequence homology with human genes. We are screening these genes experimentally to establish if they have a role in heart development and/or function. We identified 59 genes that have clear human orthologues. Genes identified included well-known ‘heart' genes, e.g. Tinman, Neuromancer, Pannier, Seven Up - thus validating our in silico strategy. One candidate heart gene identified, Fermitin 1 (Fit1) - an integrin-associated protein with 47% identity with its human orthologue (Kindlin 2) - was shown to be upregulated in the adult fly heart. Kindlin-2-/- null mouse embryos die before cardiogenesis, making it very difficult to investigate how Kindlin-2 is involved in heart development and function. We have created a Fit1 gene deletion line via imprecise P-element excision that displays semi-lethality during larval development - probably compensated for by its sister homologue in flies, Fit2. We will look at adult heart function in these mutants and, therefore, anticipate the study of fit1 animals will shed additional light on the function of this gene during development and tissue morphogenesis. With our tools, the fruit fly will be an excellent model to study the function of these genes in the adult heart and will lead to further enlightenment of their function in the mammalian heart.

Where applicable, experiments conform with Society ethical requirements