Noncanonical Hedgehog signaling

Vitam Horm. 2012;88:55-72. doi: 10.1016/B978-0-12-394622-5.00003-1.


The notion of noncanonical hedgehog (Hh) signaling in mammals has started to receive support from numerous observations. By noncanonical, we refer to all those cellular and tissue responses to any of the Hh isoforms that are independent of transcriptional changes mediated by the Gli family of transcription factors. In this chapter, we discuss the most recent findings that suggest that Patched1 can regulate cell proliferation and apoptosis independently of Smoothened (Smo) and Gli and the reports that Smo modulates actin cytoskeleton-dependent processes such as fibroblast migration, endothelial cell tubulogenesis, axonal extension, and neurite formation by diverse mechanisms that exclude any involvement of Gli-dependent transcription. We also acknowledge the existence of less stronger evidence of noncanonical signaling in Drosophila.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Arachidonic Acid / metabolism*
  • Cell Cycle / physiology*
  • Cyclin B1 / metabolism
  • Hedgehog Proteins / chemistry
  • Hedgehog Proteins / metabolism*
  • Humans
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / physiology*
  • Smoothened Receptor
  • Transcription Factors / metabolism*
  • Zinc Finger Protein GLI1


  • Cyclin B1
  • GLI1 protein, human
  • Hedgehog Proteins
  • Receptors, G-Protein-Coupled
  • SMO protein, human
  • Smoothened Receptor
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • Arachidonic Acid