Mapping Heart Development in Flies: Src42A Acts Non-Autonomously to Promote Heart Tube Formation in Drosophila

Abstract

Congenital heart defects, clinically identified in both small and large animals, are multifactorial and complex. Although heritable factors are known to have a role in cardiovascular disease, the full genetic aetiology remains unclear. Model organism research has proven valuable in providing a deeper understanding of the essential factors in heart development. For example, mouse knock-out studies reveal a role for the Integrin adhesion receptor in cardiac tissue. Recent research in Drosophila melanogaster (the fruit fly), a powerful experimental model, has demonstrated that the link between the extracellular matrix and the cell, mediated by Integrins, is required for multiple aspects of cardiogenesis. Here we test the hypothesis that Integrins signal to the heart cells through Src42A kinase. Using the powerful genetics and cell biology analysis possible in Drosophila, we demonstrate that Src42A acts in early events of heart tube development. Careful examination of mutant heart tissue and genetic interaction data suggests that Src42A’s role is independent of Integrin and the Integrin-related Focal Adhesion Kinase. Rather, Src42A acts non-autonomously by promoting programmed cell death of the amnioserosa, a transient tissue that neighbors the developing heart.

Dissecting the Role of the Extracellular Matrix in Heart Disease: Lessons from the Drosophila Genetic Model

“…Fosmid constructs may be used to insert transgenes encoding C-terminally tagged proteins [ 88 ]. The levels and localisation of these proteins can then be assessed within a living system [ 89 , 90 , 91 ].…”

Extracellular Matrix Disparities in an Nkx2-5 Mutant Mouse Model of Congenital Heart Disease

“…Integrins and gap junction proteins also play a large role in cardiac development, during which they possess dynamic spatiotemporal profiles (17,(24)(25)(26)(27). Integrins are transmembrane proteins that mediate cell-matrix interactions by serving on the cell surface as receptors for ECM ligands while connecting to the cytoskeleton and various signaling cascades on the cell interior (25).…”