Cohesinopathies are @entity1 @entity74 that include @entity17427 ( @entity17427 ) and @entity7345 ( @entity7345 ) and are characterized by defects in limb and craniofacial development as well as @entity1032 . The developmental phenotypes of @entity17427 and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that @entity7345 was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. @entity4307 stimulation of the @entity3470 pathway partially rescued translation in @entity1 @entity7345 cells and development in @entity3392 models of @entity7345 . In this study, we investigate protein translation in @entity3392 models of @entity17427 . Our results show that phosphorylation of @entity68349 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, @entity31877 and @entity31879 -morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. @entity4307 partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of @entity68349 . Concomitantly, @entity4307 treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that @entity6525 ( @entity68350 ), which is a keto derivative of @entity368 , also partially rescued the development of @entity31877 and nipbla/b morphants by boosting @entity3470 -dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the @entity3470 pathway through @entity4307 or its metabolite @entity68350 can partially rescue development in @entity3392 models for @entity17427 .

XXXX partially rescues translational and developmental defects associated with @entity3392 models of @entity17427 .

@entity1 :: ('9606', 'Species') :: ['human'] @entity1032 :: ('MESH:D008607', 'Disease') :: ['mental retardation'] @entity4307 :: ('CHEBI:15603', 'Chemical') :: ['l-leucine'] @entity368 :: ('CHEBI:25017', 'Chemical') :: ['leucine'] @entity17427 :: ('MESH:D003635', 'Disease') :: ['CdLS', 'Cornelia de Lange syndrome'] @entity31879 :: ('324475(Tax:7955)', 'Gene') :: ['smc3'] @entity7345 :: ('MESH:C535687', 'Disease') :: ['RBS', 'Roberts syndrome'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity6525 :: ('MESH:C013082', 'Chemical') :: ['alpha-ketoisocaproate'] @entity74 :: ('MESH:D030342', 'Disease') :: ['genetic disorders'] @entity68350 :: ('MESH:C081431', 'Chemical') :: ['a-KIC'] @entity31877 :: ('322275(Tax:7955)', 'Gene') :: ['rad21'] @entity3392 :: ('7955', 'Species') :: ['zebrafish'] @entity68349 :: ('445028(Tax:7955)', 'Gene') :: ['RPS6', 'RPS6 and 4EBP1']
@entity4307 :: (CHEBI:15603,Chemical) :: ['l-leucine']
