First published online February 24, 2006
Development 133, 604e (2006)
© The Company of Biologists Limited
Getting to the heart of heart development
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.
1175). 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. 1125, 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.
Related articles in Development:
- Notch1b and neuregulin are required for specification of central cardiac conduction tissue
- David J. Milan, Andrea C. Giokas, Fabrizio C. Serluca, Randall T. Peterson, and Calum A. MacRae
Development 2006 133: 1125-1132.
[Abstract]
[Full Text]
- Hand, an evolutionarily conserved bHLH transcription factor required for Drosophila cardiogenesis and hematopoiesis
- Zhe Han, Peng Yi, Xiumin Li, and Eric N. Olson
Development 2006 133: 1175-1182.
[Abstract]
[Full Text]
