Disabled-2 Is Essential for Endodermal Cell Positioning and Structure Formation during Mouse Embryogenesis☆

Developmental Biology

W.David Martin¹  Elizabeth R. Smith¹  J.David Lambeth¹  Zejuan Sheng¹  Xiang-Xi Xu¹  Thomas C. Hamilton¹  Dong-Hua Yang¹  Isabelle H. Roland¹  Junqi He¹ 

[1] Ovarian Cancer and Tumor Cell Biology Programs, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, 19111

关键词: Disabled-2;    visceral endoderm;    cell positioning/organization;    embryos;    extraembryonic endoderm;    blastocysts;    differentiation;    endocytosis;   

DOI  :  10.1006/dbio.2002.0810

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

ThesignaltransductionadapterproteinDisabled-2(Dab2)isoneofthetwomammalianorthologsoftheDrosophilaDisabled.Thebrain-specificDisabled-1(Dab1)functionsinpositionalorganizationofbraincellsduringdevelopment.Dab2iswidelydistributedandishighlyexpressedinmanyepithelialcelltypes.Thedab2genewasinterruptedbyin-frameinsertionofβ-galactosidase(LacZ)inembryonicstemcellsandtransgenicmicewereproduced.Dab2expressionwasfirstobservedintheprimitiveendodermatE4.5,immediatelyfollowingimplantation.ThehomozygousDab2-deficientmutantisembryoniclethal(earlierthanE6.5)duetodefectivecellpositioningandstructureformationofthevisceralendoderm.InE5.5dab2(−/−)conceptus,visceralendoderm-likecellsarepresentinthedeformedprimitiveeggcylinder;however,thevisceralendodermcellsarenotorganized,thecellsoftheepiblasthavenotexpanded,andtheproamnioticcavityfailstoform.Disorganizationofthevisceralendodermallayerisevident,ascellswithpositivevisceralendodermmarkersarescatteredthroughoutthedab2(−/−)conceptus.OnlydegeneratedremainswereobservedatE6.5fordab2(−/−)embryos,andbyE7.5,thedefectiveembryoswerecompletelyreabsorbed.Inblastocystinvitroculture,initiallycellswithcharacteristicsofendoderm,trophectoderm,andinnercellmasswereobservedintheoutgrowthofthehatcheddab2(−/−)blastocysts.However,thedab2(−/−)endodermalcellsaremuchmoredispersedanddisorganizedthanthosefromwild-typeblastocysts,theinnercellmassfailstoexpand,andtheoutgrowthdegeneratesbyday7.Thus,Dab2isrequiredforvisceralendodermalcellorganizationduringearlymousedevelopment.TheabsenceofanorganizedvisceralendoderminDab2-deficientconceptusleadstothegrowthfailureoftheinnercellmass.WesuggestthatDab2functionsinasignalpathwaytoregulateendodermalcellorganizationusingendocytosisofligandsfromtheblastocoelcavityasapositioningcue.

【 授权许可】

Unknown