Analysis of novel heart defects in akirin mutants

Among the metazoans the heart is one of the earliest discrete organ structures to form during embryogenesis, in a process highly conserved across the phyla. Heart development is controlled by a cascade of factors beginning with the emergence of cardiac progenitors known as cardiomyoblasts. In Drosophila melanogaster the specification of cardiac progenitors from mesoderm, differentiation and patterning of cardioblasts, and ensuing heart formation is controlled by the recursive action of the Tinman/Nkx2-5 transcription factor, which is itself initiated by the activity of the Twist bHLH transcription factor. Previous work done in the Nowak lab has identified Akirin as a highly conserved cofactor that works with Twist to selectively regulate expression of Twist target enhancers, such as mef2 and tinman. akirin mutants have a significant initial decrease in tinman expression levels as compared with wild-type embryos. akirin mutants further display profoundly abnormal hearts displaying defects in heart patterning, with disrupted organization and reduced numbers of Tinman- positive cardiomyoblasts. We have developed live imaging assays that indicate that akirin mutant hearts display profoundly abnormal contractions. Taken together, these data indicate that Akirin represents a new co-regulator of the cardiac developmental pathway, and is critical for heart patterning and formation