Early heart development is conserved from Drosophila to mammals,but this conservation is thought to break down at later developmental stages. Certainly the end products – a simple tube in flies and a multi-chambered organ in mammals – look very different. Now, though,Eric Olson's group reveal that certain later cardiogenic events are shared by flies and mammals. They show that the conserved transcription factor Hand is required for Drosophila cardiogenesis (in mammals,HAND1 and HAND2 are essential for cardiac remodelling and chamber specification) and for haematopoiesis, a previously unrecognized role (see p. ). The researchers report that Drosophila HAND is a potent transcriptional activator in vitro, and that its conversion into a transcriptional repressor blocks heart and lymph gland formation in vivo. Furthermore, embryos and larvae null for Hand have cardiac defects and lack haematopoietic progenitors,abnormalities that are prevented by the cardiac expression of Drosophila or human Hand genes. These findings indicate that Hand gene function in cardiogenesis is conserved between flies and mammals, and may also be required in mammalian haematopoiesis.
David Milan and colleagues have been investigating another aspect of heart development – the formation of the central cardiac conduction system. On p. , they report that notch1b and neuregulin are required for this process. Defects in the cardiac conduction system (which controls heart rate and rhythm) cause heart failure and sudden cardiac death. An important component of the system is the atrioventricular (AV) node, which slows down electrical impulses as they arrive at the heart's centre. The authors use several physiological assays to show that a ring of AV conduction tissue develops 40 hours after fertilization in embryonic zebrafish hearts, even under conditions of circulatory arrest – many other cardiac development events involve flow-dependent signalling. In cloche mutant fish, which lack endocardium, AV conduction tissue fails to develop, indicating that endocardial signalling is involved in its formation. Finally, morpholino knockdown experiments show that the development of AV conduction tissue requires neuregulin and notch1b. Overall, these results reveal that local endocardial/myocardial interactions are involved in patterning the central cardiac conduction tissue.
