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Science 318 (5847): 66-68

Copyright © 2007 by the American Association for the Advancement of Science

Deconstructing the Hedgehog Pathway in Development and Disease

Leni Jacob, and Lawrence Lum*

Abstract: The Hedgehog (Hh) family of secreted signaling proteins is a master regulator of cell fate determination in metazoans, contributing to both pattern formation during embryonic development and postembryonic tissue homeostasis. In a universally used mode of action, graded distribution of Hh protein induces differential cell fate in a dose-dependent manner in cells that receive Hh. Though much of this pathway has been elucidated from genetically based studies in model organisms, such as Drosophila and mice, the importance of Hh-mediated signaling in humans is clearly evident from malformations and a broad range of cancers that arise when the pathway is corrupted.

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

* To whom correspondence should be addressed. E-mail: lawrence.lum{at}

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Genome-Wide RNAi Screen Reveals Disease-Associated Genes That Are Common to Hedgehog and Wnt Signaling.
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Heparan Sulfate and Transglutaminase Activity Are Required for the Formation of Covalently Cross-linked Hedgehog Oligomers.
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Converse Conformational Control of Smoothened Activity by Structurally Related Small Molecules.
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sonic hedgehog is required in pulmonary endoderm for atrial septation.
A. D. Hoffmann, M. A. Peterson, J. M. Friedland-Little, S. A. Anderson, and I. P. Moskowitz (2009)
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GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation.
O. Nolan-Stevaux, J. Lau, M. L. Truitt, G. C. Chu, M. Hebrok, M. E. Fernandez-Zapico, and D. Hanahan (2009)
Genes & Dev. 23, 24-36
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Sonic Hedgehog signaling impairs ionizing radiation-induced checkpoint activation and induces genomic instability.
J. M. Leonard, H. Ye, C. Wetmore, and L. M. Karnitz (2008)
J. Cell Biol. 183, 385-391
   Abstract »    Full Text »    PDF »

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