Embryonic lethality in mice lacking Trim59 due to impaired gastrulation development

Abstract

ABSTRACTTRIM family members have been implicated in a variety of biological processes such as differentiation and development. We here found that Trim59 plays a critical role in early embryo development from blastocyst stage to gastrula. There existed delayed development and empty yolk sacs from embryonic day (E) 8.5 inTrim59-/- embryos. No viableTrim59-/- embryos were observed beyond E9.5. Trim59 deficiency affected primary germ layer formation at the beginning of gastrulation. InTrim59-/- embryos at E6.5 and E7.5, the expression of primary germ layer formation associated genes includingBrachyury,lefty2,Cer1,Otx2,Wnt3andBMP4was reduced. Homozygous mutant embryonic epiblast was contracted and the mesoderm was absent. Trim59 could interact with actin and myosin associated proteins. Trim59 deficiency disturbed F-actin polymerization during inner cell mass differentiation. Trim59 mediated polymerization of F-actin was via WASH K63-linked ubiquitination. Thus, Trim59 may be a critical regulator for early embryo development from blastocyst stage to gastrula through modulating F-actin assembly.