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First published online 15 February 2006
doi: 10.1242/dev.02279


Development 133, 1125-1132 (2006)
Published by The Company of Biologists 2006


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Notch1b and neuregulin are required for specification of central cardiac conduction tissue

David J. Milan1,*, Andrea C. Giokas1, Fabrizio C. Serluca2, Randall T. Peterson1 and Calum A. MacRae1

1 Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
2 Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA, USA.

* Author for correspondence (e-mail: dmilan{at}partners.org)

Accepted 10 January 2006

Normal heart function is critically dependent on the timing and coordination provided by a complex network of specialized cells: the cardiac conduction system. We have employed functional assays in zebrafish to explore early steps in the patterning of the conduction system that previously have been inaccessible. We demonstrate that a ring of atrioventricular conduction tissue develops at 40 hours post-fertilization in the zebrafish heart. Analysis of the mutant cloche reveals a requirement for endocardial signals in the formation of this tissue. The differentiation of these specialized cells, unlike that of adjacent endocardial cushions and valves, is not dependent on blood flow or cardiac contraction. Finally, both neuregulin and notch1b are necessary for the development of atrioventricular conduction tissue. These results are the first demonstration of the endocardial signals required for patterning central `slow' conduction tissue, and they reveal the operation of distinct local endocardial-myocardial interactions within the developing heart tube.

Key words: Notch, Neuregulin, Cardiac conduction system, Development, Zebrafish


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