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First published online 8 October 2008
doi: 10.1242/dev.024083

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Hedgehog signaling plays a cell-autonomous role in maximizing cardiac developmental potential

Natalie A. Thomas¹, Marco Koudijs^2,3, Fredericus J. M. van Eeden^2,3, Alexandra L. Joyner^1,* and Deborah Yelon^1,

¹ Developmental Genetics Program and Department of Cell Biology, Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
² Hubrecht Institute, Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands.
³ University of Sheffield, Department of Biomedical Science, Western Bank, Sheffield S10 2TN, UK.

Author for correspondence (e-mail: yelon{at}saturn.med.nyu.edu)

Accepted 12 September 2008

Elucidation of the complete roster of signals required for myocardial specification is crucial to the future of cardiac regenerative medicine. Prior studies have implicated the Hedgehog (Hh) signaling pathway in the regulation of multiple aspects of heart development. However, our understanding of the contribution of Hh signaling to the initial specification of myocardial progenitor cells remains incomplete. Here, we show that Hh signaling promotes cardiomyocyte formation in zebrafish. Reduced Hh signaling creates a cardiomyocyte deficit, and increased Hh signaling creates a surplus. Through fate-mapping, we find that Hh signaling is required at early stages to ensure specification of the proper number of myocardial progenitors. Genetic inducible fate mapping in mouse indicates that myocardial progenitors respond directly to Hh signals, and transplantation experiments in zebrafish demonstrate that Hh signaling acts cell autonomously to promote the contribution of cells to the myocardium. Thus, Hh signaling plays an essential early role in defining the optimal number of cardiomyocytes, making it an attractive target for manipulation of multipotent progenitor cells.

Key words: Hedgehog, Cardiac progenitor specification, Cyclopamine, Heart development, Smoothened, Zebrafish

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