Embryonic lethality in mice lacking Trim59 due to impaired gastrulation development

Xiaomin Su,Chenglei Wu,Yushuang Lin,Rongcun Yang,Zhujun Zhang,Yuan Zhang,Ming Zeng,Yongzhe Che,Xiaoying Ye,Lin Liu

doi:10.1038/s41419-018-0370-y

Xiaomin Su, Chenglei Wu + Show 8 more

Open Access

https://doi.org/10.1038/s41419-018-0370-y

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Journal: Cell Death & Disease	Publication Date: Feb 21, 2018
Citations: 11	License type: open-access

Affiliation: Nankai University, Shandong University

Abstract

TRIM 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 in Trim59−/− embryos. No viable Trim59−/− embryos were observed beyond E9.5. Trim59 deficiency affected primary germ layer formation at the beginning of gastrulation. At E6.5 and E7.5, the expression of primary germ layer formation-associated genes including Brachyury, lefty2, Cer1, Otx2, Wnt3, and BMP4 was reduced in Trim59−/− embryos. Homozygous mutant embryonic epiblasts were contracted and the mesoderm was absent. Trim59 could interact with actin- and myosin-associated proteins. Its 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.

Highlights

Mouse embryological development is a dynamic process
Trim59 deficiency causes early embryonic lethality Trim59 could be detected in murine F1 ESCs and in wild type murine E6.5-E9.5 embryos (Fig. S1), implying that Trim59 may play a role in embryonic development
In this study we found that Trim59 is a critical regulator for early embryo development from blastocyst stage to gastrula through modulating F-actin assembly

Summary

Introduction

Mouse embryological development is a dynamic process. It includes a series of cleavage divisions during development from embryonic day (E) 0.5 to E8.0 (Kojima et al, 2014). One cell embryo (E0.5) undertakes a succession of cleavage divisions to generate a blastocyst (E4.5) which contains inner cell mass (ICM) and trophectoderm (TE) (Chazaud and Rossant, 2006). The ICM contains epiblast (EPI) precursor and primitive endoderm (PrE). From E5.5 to E6.0, pre-gastrula is formed during this stage. Formation of the primitive steak (PS) marks the beginning of gastrulation at E6.5. During this stage, primary germ layers including ectoderm (EC), mesoderm (ME) and endoderm (EN) are formed (Tam et al, 2000)

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