The Hedgehog(Hh)family of secreted proteins plays essential roles in the development of a wide variety of animal species and underlies multiple human birth defects and cancers.To ensure the proper range of signaling,t...The Hedgehog(Hh)family of secreted proteins plays essential roles in the development of a wide variety of animal species and underlies multiple human birth defects and cancers.To ensure the proper range of signaling,the Hh proteins are modified with lipids,assembled into water-soluble multimers,and interact with multiple cell surface proteins.In the target cells,a largely conserved intracellular signal transduction pathway,from the cell surface receptor Patched to the Glioma-associated oncogene homolog(Gli)family of transcription factors,mediates the transcriptional responses from fruit flies to mammals.A significant divergence between vertebrates and insects is the vertebrate-specific requirement of cilia for Hh signal transduction and Gli protein activation.Finally,transcription-independent cellular responses to Hh have been described in certain developmental processes.With clinical trial underway to treat Hhrelated diseases,more work is urgently needed to reach a more comprehensive understanding of the molecular mechanisms underlying the regulation of Hh signaling in development and diseases.展开更多
文摘The Hedgehog(Hh)family of secreted proteins plays essential roles in the development of a wide variety of animal species and underlies multiple human birth defects and cancers.To ensure the proper range of signaling,the Hh proteins are modified with lipids,assembled into water-soluble multimers,and interact with multiple cell surface proteins.In the target cells,a largely conserved intracellular signal transduction pathway,from the cell surface receptor Patched to the Glioma-associated oncogene homolog(Gli)family of transcription factors,mediates the transcriptional responses from fruit flies to mammals.A significant divergence between vertebrates and insects is the vertebrate-specific requirement of cilia for Hh signal transduction and Gli protein activation.Finally,transcription-independent cellular responses to Hh have been described in certain developmental processes.With clinical trial underway to treat Hhrelated diseases,more work is urgently needed to reach a more comprehensive understanding of the molecular mechanisms underlying the regulation of Hh signaling in development and diseases.
