Key result
Sox102F silencing reduces heart rate, chamber size, and wall velocities while increasing wall thickness.
Why the study?
Genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to multiple cardiac-related endophenotypes, but its functional role in heart physiology was unclear.
Silencing the Drosophila ortholog of SOX5 leads to severe cardiac dysfunction and structural defects, suggesting that alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases.
These Drosophila findings are hypothesis-generating; clinical translation to human cardiomyopathy remains unproven.
The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quantitatively measure cardiac function in adult flies. For this purpose, we have developed a high-speed and ultrahigh-resolution optical coherence tomography imaging system, which enables rapid cross-sectional imaging of the heart tube over various cardiac cycles for the measurement of cardiac structural and dynamical parameters such as HR, dimensions and areas of heart chambers, cardiac wall thickness and wall velocities. We have found that the silencing of Sox102F resulted in a significant decrease in HR, heart chamber size and cardiac wall velocities, and a significant increase in cardiac wall thickness that was accompanied by disrupted myofibril structure in adult flies. In addition, the silencing of Sox102F in the wing led to increased L2, L3 and wing marginal veins and increased and disorganized expression of wingless, the central component of the Wnt signaling pathway. Collectively, the silencing of Sox102F resulted in severe cardiac dysfunction and structural defects with disrupted Wnt signaling transduction in flies. This implicates an important functional role for SOX5 in heart and suggests that the alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases or traits.
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Li et al. (2013) studied Cardiac function. Silencing of Sox102F was evaluated on Cardiac structural and dynamical parameters (HR, dimensions, areas, wall thickness, wall velocities). Silencing of the Drosophila ortholog Sox102F resulted in a significant decrease in heart rate, chamber size, and wall velocities, and an increase in cardiac wall thickness.
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