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Sci. Signal., 16 October 2012
Vol. 5, Issue 246, p. re6
[DOI: 10.1126/scisignal.2002906]

REVIEWS

The Hedgehog Signal Transduction Network

David J. Robbins1,2,3*, Dennis Liang Fei1, and Natalia A. Riobo4*

1 Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
2 Sylvester Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
3 Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
4 Department of Biochemistry and Molecular Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Abstract: Hedgehog (Hh) proteins regulate the development of a wide range of metazoan embryonic and adult structures, and disruption of Hh signaling pathways results in various human diseases. Here, we provide a comprehensive review of the signaling pathways regulated by Hh, consolidating data from a diverse array of organisms in a variety of scientific disciplines. Similar to the elucidation of many other signaling pathways, our knowledge of Hh signaling developed in a sequential manner centered on its earliest discoveries. Thus, our knowledge of Hh signaling has for the most part focused on elucidating the mechanism by which Hh regulates the Gli family of transcription factors, the so-called "canonical" Hh signaling pathway. However, in the past few years, numerous studies have shown that Hh proteins can also signal through Gli-independent mechanisms collectively referred to as "noncanonical" signaling pathways. Noncanonical Hh signaling is itself subdivided into two distinct signaling modules: (i) those not requiring Smoothened (Smo) and (ii) those downstream of Smo that do not require Gli transcription factors. Thus, Hh signaling is now proposed to occur through a variety of distinct context-dependent signaling modules that have the ability to crosstalk with one another to form an interacting, dynamic Hh signaling network.

* To whom correspondence should be addressed. E-mail: drobbins{at}med.miami.edu (D.J.R.); natalia.riobo{at}jefferson.edu (N.A.R.)

Citation: D. J. Robbins, D. L. Fei, N. A. Riobo, The Hedgehog Signal Transduction Network. Sci. Signal. 5, re6 (2012).

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