Tailup plays multiple roles during cardiac outflow assembly in Drosophila.

The Drosophila LIM-homeodomain transcription factor Tailup and its vertebrate counterpart Islet1 are expressed in cardiac progenitor cells where they play a specification role. Loss of function of Islet1 leads to a complete absence of the right ventricle and affects the development of the cardiac outflow tract in mouse embryos. Similarly, tailup mutant embryos display a reduced number of cardiac cells but the role of tailup in cardiac outflow formation in Drosophila remains unknown. Here, we show that tailup is expressed in the main Drosophila cardiac outflow components, i.e., heart anchoring cells (HANC) and cardiac outflow muscles (COM) and that loss of its function and/or tissue-specific knockdowns dramatically affect cardiac outflow morphogenesis. Our data demonstrate that tailup plays many roles and is required for the acquisition of HANC and COM properties. We also show that tailup regulates HANC motility, COM shapes and their attachment to the heart tip and genetically interacts with ladybird, shotgun and slit, which are known to be involved in cardiac outflow assembly. Furthemore, using tissue-specific overexpression of dominant negative tailup constructs lacking sequences encoding either the homeodomain or the LIM domain, we demonstrate that tailup can exert its function not only in transcription factor mode but also via its protein-protein interaction domain. We identify Tailup as an evolutionarily-conserved regulator of cardiac outflow formation and provide further evidence for its conserved role in heart development.