Developmental Biology | |
Disabled-2 Is Essential for Endodermal Cell Positioning and Structure Formation during Mouse Embryogenesis☆ | |
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
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201912090729298ZK.pdf | 99KB | download |