Impaired primitive erythropoiesis and defective vascular development in Trim71-KO embryos

Life Sci Alliance. 2025 Feb 5;8(4):e202402956. doi: 10.26508/lsa.202402956. Print 2025 Apr.

Abstract

The transition of an embryo from gastrulation to organogenesis requires precisely coordinated changes in gene expression, but the underlying mechanisms remain unclear. The RNA-binding protein Trim71 is essential for development and serves as a potent regulator of post-transcriptional gene expression. Here, we show that global deficiency of Trim71 induces severe defects in mesoderm-derived cells at the onset of organogenesis. Murine Trim71-KO embryos displayed impaired primitive erythropoiesis, yolk sac vasculature, heart function, and circulation, explaining the embryonic lethality of these mice. Tie2 Cre Trim71 conditional knockout did not induce strong defects, showing that Trim71 expression in endothelial cells and their immediate progenitors is dispensable for embryonic survival. scRNA-seq of E7.5 global Trim71-KO embryos revealed that transcriptomic changes arise already at gastrulation, showing a strong up-regulation of the mesodermal pioneer transcription factor Eomes. We identify Eomes as a direct target of Trim71-mediated mRNA repression via the NHL domain, demonstrating a functional link between these important regulatory genes. Taken together, our data suggest that Trim71-dependent control of gene expression at gastrulation establishes a framework for proper development during organogenesis.

MeSH terms

  • Animals
  • Embryo, Mammalian / metabolism
  • Embryonic Development / genetics
  • Endothelial Cells / metabolism
  • Erythropoiesis* / genetics
  • Female
  • Gastrulation / genetics
  • Gene Expression Regulation, Developmental
  • Mesoderm / metabolism
  • Mice
  • Mice, Knockout
  • Organogenesis / genetics
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Transcription Factors
  • Tripartite Motif Proteins* / genetics
  • Tripartite Motif Proteins* / metabolism
  • Ubiquitin-Protein Ligases* / genetics
  • Ubiquitin-Protein Ligases* / metabolism
  • Yolk Sac / metabolism

Substances

  • T-Box Domain Proteins
  • ER71 protein, mouse
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases
  • Transcription Factors