Neural crest invasion is a spatially-ordered progression into the head with higher cell proliferation at the migratory front as revealed by the photoactivatable protein, KikGR

摘要

Neuralcrestcell(NCC)invasionisacomplexsculptingofindividualcellsintoorganizedmigratorystreamsthatleadtoorgandevelopmentalongthevertebrateaxis.KeytoourunderstandingofhowmolecularmechanismsmodulatetheNCCmigratorypatternisinformationaboutcellbehaviors,yetithasbeenchallengingtoselectivelymarkandanalyzemigratoryNCCsinalivingembryo.Here,weapplyaninnovativeinvivostrategytoinvestigatechickNCCbehaviorswithintherhombomere4(r4)migratorystreambycombiningphotoactivationofKikGRandconfocaltime-lapseanalysisofH2B-mRFP1transfectedNCCs.Wefindthatthespatialorderofr4NCCemergencetranslatesintoadistal-to-proximalinvasionofthe2ndbranchialarch.LeadandtrailingNCCsdisplaysimilaraveragecellspeedsanddirectionalities.Surprisingly,wefindthatleadNCCsproliferatealongthemigratoryrouteandgrowtooutnumbertrailingNCCsbynearly3to1.Asimple,cell-basedcomputationalmodelreproducesther4NCCmigratorypatternandpredictstheinvasionordercanbedisruptedbyslower,lessdirectionalleadcellsorbyenvironmentalnoise.OurresultssuggestamodelinwhichNCCbehaviorsmaintainaspatially-orderedinvasionofthebranchialarcheswithdifferencesincellproliferationbetweenthemigratoryfrontandtrailingNCCs./p/div