The Hedgehog signal transduction network.
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.
Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. drobbins@med.miami.edu
David J
DJ
Robbins
Dennis Liang
DL
Fei
Natalia A
NA
Riobo
D000818:Animals; D002923:Cilia / Q000502:physiology; D015509:Developmental Biology / Q000379:methods; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015513:Oncogene Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D015513:Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C100664:smo protein, Drosophila; D046988:Proteasome Endopeptidase Complex