Notch Signalling Synchronizes the Zebrafish Segmentation Clock but Is Not Needed To Create Somite Boundaries 英文参考文献.docVIP
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Notch Signalling Synchronizes the Zebrafish Segmentation Clock but Is Not Needed To Create Somite Boundaries 英文参考文献
NotchSignallingSynchronizestheZebrafish
SegmentationClockbutIsNotNeeded
ToCreateSomiteBoundaries
Ertug?rul M.Ozbudak¨ ¤,Julian Lewis*
VertebrateDevelopmentLaboratory,CancerResearchUKLondonResearchInstitute,London,UnitedKingdom
Somitesegmentationdependsonageneexpressionoscillatororclockintheposteriorpresomiticmesoderm(PSM)and
onread-outmachineryintheanteriorPSMtoconvertthepatternofclockphasesintoasomitepattern.Notchpathway
mutationsdisruptsomitogenesis,andpreviousstudieshavesuggestedthatNotchsignallingisrequiredbothforthe
oscillations and for the read-out mechanism. Byblocking or overactivating theNotch pathwayabruptly at different
times,weshowthatNotchsignallinghasnoessentialfunctionintheanteriorPSMandisrequiredonlyintheposterior
PSM,whereitkeepstheoscillationsofneighbouringcellssynchronized.UsingaGFPreporterfortheoscillatorgene
her1,wemeasuretheinfluenceofNotchsignallingonher1expressionandshowbymathematicalmodellingthatthisis
sufficientforsynchronization.Ourmodel,inwhichintracellularoscillationsaregeneratedbydelayedautoinhibitionof
her1andher7andsynchronizedbyNotchsignalling,explainstheobservationsfully,showingthattherearenogrounds
toinvokeanyadditionalrolefortheNotchpathwayinthepatterningofsomiteboundariesinzebrafish.
Citation:O¨zbudakEM,LewisJ(2008)Notchsignallingsynchronizesthezebrafishsegmentationclockbutisnotneededtocreatesomiteboundaries.PLoSGenet4(2):e15.
doi:10.1371/journal.pgen.0040015
in a manner not yet fully understood, create the ?nal
segmentation pattern that becomes manifest as the cells at
Introduction
Thesegmentsofthevertebratetrunkandtailoriginatefrom
aseriesofblocksoftissue,thesomites,thatareformedoneach
sideofthebodyaxisduringearlydevelopment.Mutationsin
theNotchcell-cellsignallingpathwaydisruptsomiteformation
andleadtoanirregularlysegmentedbodyaxis[1–14].Buthow
do they cause this effect? What speci?c part does Notch
signallingplayincreatingtheregularsomitepattern?
last emerge from the PSM and halt their oscillations
(reviewedin[14,2
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