MATERNAL CONTROL OF NODAL SIGNALING: REGULATION OF SQUINT TRANSLATION

Abstract

Nodal signaling is critical for embryonic germ layer patterning, axis formation, and maintenance of human embryonic stem cell pluripotency. Precise and timely regulation of Nodal signaling is critical since deregulated signaling is associated with metastasizing tumors. Here, we show that translational control by maternal Y box-binding protein 1 (Ybx1) regulates Nodal signaling. We biochemically identified Ybx1 as an RNA-binding factor that recognizes the 3¿ un-translated region (UTR) of zebrafish nodal related-1/squint (sqt) RNA. Maternal Ybx1 is essential for zebrafish embryogenesis. Importantly, sqt/nodal RNA localization is disrupted, and Sqt protein translation is premature in ybx1 mutant embryos, leading to unregulated Nodal signaling. Consequently, mutant embryos have excess extra-embryonic cells, and fail to initiate gastrulation. These findings show that Ybx1 prevents ectopic Nodal signaling by translational repression of maternal nodal RNA, and reveal a new paradigm in regulation of Nodal signaling, which is likely to be conserved.