TY  - JOUR
AU  - Beckröge, Tobias
AU  - Jux, Bettina
AU  - Seifert, Hannah
AU  - Theobald, Hannah
AU  - De Domenico, Elena
AU  - Paulusch, Stefan
AU  - Beyer, Marc
AU  - Schlitzer, Andreas
AU  - Mass, Elvira
AU  - Kolanus, Waldemar
TI  - Impaired primitive erythropoiesis and defective vascular development in Trim71-KO embryos.
JO  - Life science alliance
VL  - 8
IS  - 4
SN  - 2575-1077
CY  - Heidelberg
PB  - EMBO Press
M1  - DZNE-2025-00300
SP  - e202402956
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Erythropoiesis: genetics
KW  - Mice
KW  - Mice, Knockout
KW  - Gene Expression Regulation, Developmental: genetics
KW  - Embryo, Mammalian: metabolism
KW  - Organogenesis: genetics
KW  - Yolk Sac: metabolism
KW  - Yolk Sac: blood supply
KW  - Yolk Sac: embryology
KW  - T-Box Domain Proteins: genetics
KW  - T-Box Domain Proteins: metabolism
KW  - Gastrulation: genetics
KW  - Endothelial Cells: metabolism
KW  - Female
KW  - RNA-Binding Proteins: metabolism
KW  - RNA-Binding Proteins: genetics
KW  - Mesoderm: metabolism
KW  - Mesoderm: embryology
KW  - T-Box Domain Proteins (NLM Chemicals)
KW  - RNA-Binding Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39909558
DO  - DOI:10.26508/lsa.202402956
UR  - https://pub.dzne.de/record/276481
ER  -