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由于原肠胚发育受损，Trim59 缺失的小鼠胚胎致死。

Embryonic lethality in mice lacking Trim59 due to impaired gastrulation development.

机构信息

Department of Immunology Nankai University School of Medicine, Nankai University, Tianjin, China.

Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, China.

出版信息

Cell Death Dis. 2018 Feb 21;9(3):302. doi: 10.1038/s41419-018-0370-y.

DOI:10.1038/s41419-018-0370-y
PMID:29467473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5833458/
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.

摘要

TRIM 家族成员参与了多种生物学过程，如分化和发育。我们在这里发现 Trim59 在囊胚期到原肠胚期的早期胚胎发育中起着关键作用。Trim59-/-胚胎从胚胎第 8.5 天开始出现发育迟缓，卵黄囊为空。在 E9.5 之后，没有观察到存活的 Trim59-/-胚胎。Trim59 缺失会影响原肠胚形成早期的初级胚层形成。在 E6.5 和 E7.5，Trim59-/-胚胎中初级胚层形成相关基因的表达，包括 Brachyury、lefty2、Cer1、Otx2、Wnt3 和 BMP4，减少。同源突变胚胎外胚层收缩，中胚层缺失。Trim59 可以与肌动蛋白和肌球蛋白相关蛋白相互作用。其缺失干扰了内细胞团分化过程中的 F-actin 聚合。Trim59 通过 WASH K63 连接的泛素化调节 F-actin 的聚合。因此，Trim59 可能通过调节 F-actin 组装，成为从囊胚期到原肠胚期早期胚胎发育的关键调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/bc2de19b6e96/41419_2018_370_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/59bf5cdcebb6/41419_2018_370_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/e7e067417809/41419_2018_370_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/d5f65506fbdc/41419_2018_370_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/8b6eaef4c542/41419_2018_370_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/8eeeed639d1c/41419_2018_370_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/9873bf05c33f/41419_2018_370_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/bc2de19b6e96/41419_2018_370_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/59bf5cdcebb6/41419_2018_370_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/e7e067417809/41419_2018_370_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/d5f65506fbdc/41419_2018_370_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/8b6eaef4c542/41419_2018_370_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/8eeeed639d1c/41419_2018_370_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/9873bf05c33f/41419_2018_370_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0e/5833458/bc2de19b6e96/41419_2018_370_Fig7_HTML.jpg

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