Arx is required for normal enteroendocrine cell development in mice and humans

摘要

Enteroendocrinecellsofthegastrointestinal(GI)tractplayacentralroleinmetabolism,digestion,satietyandlipidabsorption,yettheirdevelopmentremainspoorlyunderstood.HereweshowthatArx,ahomeodomain-containingtranscriptionfactor,isrequiredforthenormaldevelopmentofmouseandhumanenteroendocrinecells.ArxexpressionisdetectedinasubsetofNeurogenin3(Ngn3)-positiveendocrineprogenitorsandisalsofoundinasubsetofhormone-producingcells.Inmice,removalofemArx/emfromthedevelopingendodermresultsinadecreaseofenteroendocrinecelltypesincludinggastrin-,glucagon/GLP-1-,CCK-,secretin-producingcellpopulationsandanincreaseofsomatostatin-expressingcells.Thisphenotypeisalsoobservedinmicewithendocrine-progenitor-specificemArx/emablationsuggestingthatemArx/emisrequiredintheprogenitorforenteroendocrinecelldevelopment.Inaddition,depletionofhumanemARX/emindevelopinghumanintestinaltissueresultsinaprofounddeficitinexpressionoftheenteroendocrinecellmarkersCCK,secretinandglucagonwhileexpressionofapan-intestinalepithelialmarker,CDX2,andothernon-endocrinemarkersremainedunchanged.Takentogether,ourfindingsuncoveranovelandconservedroleofemArx/eminmammalianendocrinecelldevelopmentandprovideapotentialcauseforthechronicdiarrheaseeninbothhumansandmicecarryingemArx/emmutations./p/div