Inhibition of BMP signaling during zebrafish fin regeneration disrupts fin growth and scleroblast differentiation and function

摘要

Thezebrafishcaudalfinprovidesasimplemodeltostudymolecularmechanismsofdermalboneregeneration.WepreviouslyshowedthatmisexpressionofBonemorphogeneticprotein2b(Bmp2b)inducesectopicboneformationwithintheregenerate.Hereweshowthatinadditiontoembmp2b/emandembmp4/emanotherfamilymember,embmp6/em,isinvolvedinfinregeneration.WefurtherinvestigatedthefunctionofBMPsignalingbyectopicallyexpressingtheBMPsignalinginhibitorChordinwhichcaused:(1)inhibitionofregenerateoutgrowthduetoadecreaseofblastemacellproliferationanddownregulationofemmsxb/emandemmsxC/emexpressionand(2)reducedbonematrixdepositionresultingfromadefectinthematurationandfunctionofbone-secretingcells.WethenidentifiedtargetsofBMPsignalinginvolvedinregenerationoftheboneofthefinrays.emrunx2a/b/emandtheirtargetemcol10a1/emweredownregulatedfollowingBMPsignalinginhibition.Unexpectedly,theemsox9a/b/emtranscriptionfactorsresponsibleforchondrocytedifferentiationweredetectedinthenon-cartilaginousfinrays,emsox9a/emandemsox9b/emwerenotonlydifferentiallyexpressedbutalsodifferentiallyregulatedsinceemsox9a/em,butnotemsox9b/em,wasdownregulatedintheabsenceofBMPsignaling.Finally,thisanalysisrevealedthesurprisingfindingoftheexpression,inthefinregenerate,ofseveralfactorswhicharenormallythesignaturesofchondrogenicelementsduringendochondralboneformationalthoughfinraysformthroughdermalossification,withoutacartilageintermediate./p/div