Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development

摘要

emHesx1/emhasbeenshowntobeessentialfornormalpituitarydevelopment.ThehomeoboxgeneemSix3/emisexpressedinthedevelopingpituitaryglandduringmousedevelopmentbutitsfunctioninthistissuehasbeenprecludedbythefactthatintheemSix3/em-deficientembryosthepituitaryglandisnotinduced.TogaininsightsintothefunctionofemSix3/emduringpituitarydevelopmentwehavegeneratedemSix3sup+/minus;/sup;Hesx1supCre/+/sup/emdoubleheterozygousmice.Strikingly,thesemiceshowmarkeddwarfism,whichisfirstdetectablearoundweaning,anddiebythe5thndash;6thweekofage.Thyroidandgonaddevelopmentisalsoimpairedintheseanimals.AnalysisofemSix3sup+/minus;/sup;Hesx1supCre/+/sup/emcompoundembryosindicatesthathypopituitarismisthelikelycauseofthesedefectssincepituitarydevelopmentisseverelyimpairedinthesemutants.SimilartotheemHesx1/em-deficientembryos,Rathke'spouchisinitiallyexpandedinemSix3sup+/minus;/sup;Hesx1supCre/+/sup/emcompoundembryosduetoanincreaseincellproliferation.Subsequently,theanteriorpituitaryglandappearsbifurcated,dysmorphicandoccasionallyectopicallymisplacedinthenasopharyngealcavity,butcelldifferentiationisunaffected.OurresearchhasrevealedaroleforemSix3/eminnormalpituitarydevelopment,whichhaslikelybeenconservedduringevolutionasemSIX3/emisalsoexpressedinthepituitaryglandofthehumanembryo./p/div