Loss of Tbx2 delays optic vesicle invagination leading to small optic cups

摘要

emTbx2/emisaT-boxtranscriptionfactorgenethatisdynamicallyexpressedinthepresumptiveretinaduringopticvesicleinvagination.SeveralfindingsimplicateemTbx2/emincellcycleregulation,includingitsoverexpressionintumoursandregulationofproliferationduringheartdevelopment.WeinvestigatedtheroleofemTbx2/eminopticcupformationbyanalysingmicewithatargetedhomozygousmutationinemTbx2/em.LossofTbx2causedareducedpresumptiveretinalvolumeduetoincreasedapoptosis,andadelayinventralopticvesicleinvaginationleadingtotheformationofsmallandabnormallyshapedopticcups.emTbx2/emisessentialformaintenance,butnotinductionofexpressionofthedorsalretinaldeterminant,emTbx5/em,andactsdownstreamofemBmp4/em,adorsallyexpressedgeneimplicatedinhumanmicrophthalmia.Thesmallretinashowedahypocellularventralregion,lossofemFgf15/em,normallyexpressedinproliferatingcentralretinalcells,andincreasednumbersofmitoticcellsinthedorsalregion,indicatingthatemTbx2/emisrequiredfornormalgrowthanddevelopmentacrosstheDndash;Vaxis.Dorsalexpressionofpotentialregulatorsofretinalgrowth,emCyp1b1/emandCx43,andthetopographicguidancemoleculeemephrinB2/em,wasincreased,andintraretinalaxonsweredisorganisedresultinginafailureofopticnerveformation.OurdataprovideevidencethatemTbx2/emisrequiredforproperopticcupformationandplaysacriticalearlyroleinregulatingregionalretinalgrowthandtheacquisitionofshapeduringopticvesicleinvagination./p/div