SnapShot:HedgehogSignalingPathwayMiao-HsuehChen,ChristopherW.Wilson,andPao-TienChuangCardiovascularResearchInstitute,UniversityofCalifornia,SanFrancisco,CA94158,USA386Cell130,July27,2007©2007ElsevierInc.DOI10.1016/j.cell.2007.07.017Seeonlineversionforlegend,abbreviations,andreferences.TheHedgehog(Hh)signaltransductionpathwaycontrolsnumerousprocessesduringflyandvertebrateembryonicdevelopmentandadulthomeostasis,includingtissue/organpatterning,cellularproliferationanddifferentiation,pathfinding,left/rightasymmetry,andstemcellmaintenance.Hhsignalingisdysregulatedinseveralcongenitaldefectsandmanytypesoftumors.Hhisabletosignalatshort-rangebutalsomayactasalong-rangemorphogeninmultiplecontexts(thisaspectiscontrolledinpartbylipidmodificationoftheHhmolecule).HhsignalingcontrolsthebalanceofthetranscriptionalactivatorandrepressorformsofCi/Gli,theratiosofwhichareessentialforinterpretingthelevelofHhsignalinamorphogeneticfieldandforgeneratingdiverseoutputs.Hh-ProducingCellAftertranslation,theHhprecursorenterstheER/Golgisecretorypathway.AutoproteolysismediatedbytheC-terminalofHh(Hh-C)releasestheN-terminalsignalingpeptide(Hh-N),withcholesterolcovalentlylinkedtoitsCterminus.AdditionofapalmitatemoietytotheNterminusoftheHhsignalingfragmentiscatalyzedbySkinnyhedgehog(Ski/Skn).LipidmodificationsareessentialfortheHhligandtoinducehigh-levelsignalingactivityandproperformationofamorphogengradient.LipidatedHhisassistedinitsreleasefromcellsbyDispatchedandpossiblybytheheparansulfateproteoglycans(HSPGs)DallyandDally-like(Dlp)andcanbedetectedindis-tantHh-responsivecells.AlthoughthemechanismoflipidatedHh-Nreleaseintotheextracellularmatrixisunknown,twosolubleformsoflipidatedHh-Nhavebeendetectedincludingamultimericproteincomplexinbothfliesandvertebratesandalipoproteinparticleinflies.Inflies,HhintheextracellularmatrixisprotectedfromdegradationbyShifted(Shf)andisfunneledtoitsdestinationbyDlp.SpecificHSPGcoreproteinsmayplayaroleinvertebrateHhsignaling,butthishasnotyetbeenshown.Hh-RespondingCellHhel...
