Abstract
Liver organogenesis begins with hepatic precursors in the foregut endoderm, followed by hepatoblast specification, differentiation, outgrowth, and maturation for the formation of functional hepatocytes. Although several signaling pathways and critical factors that regulate liver specification, differentiation, and proliferation have been identified, little is known about how liver maturation is regulated. Here, we used a screen for mutations affecting liver development in zebrafish and identified a cq96 mutant that exhibits a specific defect in liver maturation. Results from positional cloning revealed that cq96 encodes an RNA-binding protein, Rbm15, which is an evolutionarily conserved Spen family protein and known to play a crucial role in RNA m6A modification, nuclear export, and alternative splicing. However, a function of Rbm15 in embryonic liver development has not been reported. We found that Rbm15 is specifically expressed in the liver after its differentiation. CRISPR/Cas9-mediated loss of rbm15 repressed hepatic maturation, but did not affect hepatoblast specification, differentiation, and hepatocyte proliferation and apoptosis. Additional experiments disclosed that the mTOR complex 1 (mTORC1) pathway is highly activa...Continue Reading
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