Dysregulation of gene expression during gastrulation results in impaired primitive erythropoiesis and vascular development in Trim71-KO embryos
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The transition of an embryo from gastrulation to organogenesis requires precisely coordinated changes in gene expression. The RNA-binding protein Trim71 is essential for embryonic survival, but its exact role in mammalian development in vivo remains poorly defined. Here we show that murine Trim71 -KO embryos appear normal until embryonic day (E)8.5 but display severe defects in primitive erythropoiesis, yolk sac vasculature and heart function during the onset of organogenesis at E9.5 and E10.5. This led to an impaired vascular translocation of yolk sac-derived macrophage progenitors to the embryo head, independent of Trim71 expression in erythro-myeloid progenitors. The cardiovascular and erythropoiesis defects explain the embryonic lethality upon global Trim71 -KO. Targeting Trim71 in hematoendothelial progenitors did not induce strong developmental defects, indicating an earlier developmental origin of these phenotypes in Trim71 -KO embryos. ScRNA-seq of E7.5 Trim71 -KO embryos revealed that transcriptomic changes arise already at gastrulation, showing a strong upregulation of the transcription factor Eomes. We identify Eomes as a direct target of Trim71-mediated mRNA repression via the NHL domain, demonstrating a functional link of Trim71 to a key regulator of mesodermal development. Taken together, our data suggest that Trim71-dependent control of gene expression at gastrulation establishes a framework for proper development during organogenesis.