Spots and stripes: Pleomorphic patterning of stem cells via p-ERK-dependent cell chemotaxis shown by feather morphogenesis and mathematical simulation

摘要

Akeyissueinstemcellbiologyisthedifferentiationofhomogeneousstemcellstowardsdifferentfateswhicharealsoorganizedintodesiredconfigurations.Littleisknownaboutthemechanismsunderlyingtheprocessofperiodicpatterning.Featherexplantsofferafundamentalandtestablemodelinwhichmulti-potentialcellsareorganizedintohexagonallyarrangedprimordiaandthespacingbetweenprimordia.PreviousworkexploredrolesofaTuringreactionndash;diffusionmechanisminestablishingchemicalpatterns.Hereweshowthatacontinuumoffeatherpatterns,rangingfromstripestospots,canbeobtainedwhenthelevelofp-ERKactivityisadjustedwithchemicalinhibitors.Thepatternsaredose-dependent,tissuestage-dependent,andirreversible.AnalysesshowthatERKactivity-dependentmesenchymalcellchemotaxisisessentialforconvertingmicro-signalingcentersintostablefeatherprimordia.Amathematicalmodelbasedonshort-rangeactivation,long-rangeinhibition,andcellchemotaxisisdevelopedandshowntosimulateobservedexperimentalresults.Thisgenericcellbehaviormodelcanbeappliedtomodelstemcellpatterningbehavioratlarge./p/div