Retinoic Acid Induces Stage-Specific Repatterning of the Rostral Central Nervous System

摘要

Wehadpreviouslyreportedthatingastrulatingmouseembryosretinoicacid(RA)inducesmorphologicalaswellmolecularalterationsstrictlydependingonthetimeofadministration.Inparticular,embryostreatedwithRAatthemidndash;latestreakstagesharereductionoftherostralcentralnervoussystem(CNS)andincreaseofthehindbrain.Inthesameembryos,lossoftheforebrain-expressedgenes,suchasemEmx1,Emx2,/emandemDlx1,/emandrostralectopicexpressionoftheemHoxb-1/emgenesuggestanantero-posterior(A/P)orderedrepatterningofthefore-,mid-,andhindbrainregions.Severalgenes,suchasemPax-2,Wnt-1,En-2,/emandemEn-1,/emareinvolvedintheestablishmentofmidbrainandrostralhindbrainregionalidentitiesandboundaries.WereportthatthesegenesbecomecoordinatelyanteriorizedonlyinembryostreatedwithRAatthelatestreakstage.Moreover,inthehindbrainofthesameembryos,at8.5dayspostcoitum(dpc),emWnt-1/emandemPax-2/emarerostrallyinducedallalongtheneuralplate.ConsideringthatforebrainmarkersarerepressedinembryostreatedwithRAatthesametime,thesefindingsstronglysupporttheideathatRAadministrationatthelatestreakstageinducesanorderedrepatterningoftherostralCNS,possiblyalteringtheA/Pnatureofmesendodermalinductivesignals./p/div