Epithelia–Mesenchyme Interaction Plays an Essential Role in Transdifferentiation of Retinal Pigment Epithelium of silver Mutant Quail: Localization of FGF and Related Molecules and Aberrant Migration Pattern of Neural Crest Cells during Eye Rudiment Formation

摘要

Homozygotesofthequailsilvermutation,whichhaveplumagecolorchanges,alsodisplayauniquephenotypeintheeye:duringearlyembryonicdevelopment,theretinalpigmentepithelium(RPE)spontaneouslytransdifferentiatesintoneuralretinaltissue.Mitfisconsideredtobetheresponsiblegeneandtofunctionsimilarlytothemousemicrophthalmiamutation,andtissueinteractionbetweenRPEandsurroundingmesenchymaltissueinorganculturehasbeenshowntobeessentialfortheinitiationofthetransdifferentiationprocessinwhichfibroblastgrowthfactor(FGF)signalingisinvolved.Theimmunohistochemicalresultsofthepresentstudyshowthatlamininandheparansulfateproteoglycan,bothactingascofactorsforFGFbinding,arelocalizedintheareaoftransdifferentiationofsilverembryosmuchmoreabundantlythaninwild-typeembryos.MoreintenseimmunohistochemicalstainingwithFGF-1antibody,butnotwithFGF-2antibody,isalsofoundintheneuralretina,RPE,andchoroidaltissueofsilverembryosthaninwild-typeembryos.HNK-1immunohistochemistryrevealedthatclustersofHNK-1-positivecells(presumptivemigratingneuralcrestcells)arefrequentlylocatedaroundthedevelopingeyesandintheposteriorregionofthesilverembryoniceye.Finally,chicka€“quailchimericaleyesweremadebygraftingsilverquailopticvesiclestochickenhostembryos:inmostcases,notransdifferentiationoccursinthesilverRPE,butinafewcases,transdifferentiationoccurswheresilverquailcellspredominateinthechoroidtissue.TheseobservationstogetherwithourpreviousinvitrostudyindicatethatthesilvermutationaffectsnotonlyRPEcellsbutalsocephalicneuralcrestcells,whichmigratetotheeyerudiment,andthatthesecrestcellsplayanessentialroleinthetransdifferentiationofRPE,possiblybymodifyingtheFGFsignalingpathway.TheprecisemolecularmechanisminvolvedinRPEa€“neuralcrestcellinteractionisstillunknown,andthequailsilvermutationisconsideredtobeagoodexperimentalmodelforstudyingtheroleofneuralcrestcellsinvertebrateeyedevelopment.