Regulatory mechanism of Pabpc1a during zebrafish vasculogenesis.

Abstract

Vascular development begins with vasculogenesis during early embryogenesis. This process is controlled by a highly integrated, multi-layered molecular network. However, the role of post-transcriptional regulation in this context remains poorly understood. Cytoplasmic poly(A) binding protein 1a (Pabpc1a) is a key RNA-binding protein that regulates gene expression at the post-transcriptional level and participates in many physiological and pathological processes. Its role in vascular development, however, is still unclear. In this study, we first found that pabpc1a is highly expressed in endothelial cells during the critical window of vasculogenesis. We then generated a pabpc1a knockout model using CRISPR/Cas9. Functional analyses showed that loss of pabpc1a disrupted the expression of genes involved in arterial-venous specification and altered the arterial-to-venous diameter ratio. In contrast, overexpression of pabpc1a effectively rescued the vascular defects. Mechanistically, transcriptomic analysis revealed widespread gene expression changes in endothelial cells lacking pabpc1a. Pathways related to translation, ribosome biogenesis, and energy metabolism were significantly downregulated. These findings suggest that Pabpc1a regulates vasculogenesis by coordinating protein synthesis and metabolic homeostasis. In summary, our study demonstrates Pabpc1a as an essential post-transcriptional regulator during vasculogenesis and provides new insight into the regulatory network governing vascular development.