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Am J Physiol Gastrointest Liver Physiol 294: G844-G849, 2008. First published January 31, 2008; doi:10.1152/ajpgi.00564.2007
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THEMES

The Adventures of Sonic Hedgehog in Development and Repair. III. Hedgehog processing and biological activity

Shohreh F. Farzan,1 Samer Singh,1 Neal S. Schilling,1 and David J. Robbins1,2

1Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire; and 2Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire

Submitted 4 December 2007 ; accepted in final form 28 January 2008

The Hedgehog (Hh) family of secreted proteins is necessary for aspects of the development and maintenance of the gastrointestinal tract. Hh is thought to function as a morphogen, a mitogen, a cell survival factor, and an axon guidance factor. Given its wide role in development, as well as in a variety of disease states, understanding the regulation of Hh function and activity is critically important. However, the study of Hh signaling has been impeded by its unusual biology. Hh is unique in that it is the only protein covalently modified by cholesterol, which in turn affects numerous aspects of its localization, release, movement, and activity. All are important factors when considering Hh's physiological role, and animals have developed an intricate system of regulators responsible for both promoting and inhibiting the activity of Hh. This review is intended to give a broad overview of how the biosynthesis and movement of Hh contributes to its biological activity.

morphogen; review


Address for reprint requests and other correspondence: D. J. Robbins, 607 Remsen HB 7650, Hanover, NH 03755 (e-mail: david.j.robbins{at}dartmouth.edu)






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