Yap1/Taz are essential for the liver development in zebrafish

Highlights: • Taz is significantly up-regulated in zebrafish yap1 mutants. • yap1^−/−; taz^+/− embryos are defective in digestive organs development. • Mutations in yap1^−/−; taz^+/− impair cell proliferation in liver and movement of LPM. • Taz can substituteYap1's function in liver development in zebrafish. Hippo pathway regulates cell proliferation and differentiation. Yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) are effectors of Hippo pathway. The function of Yap/Taz in embryonic liver development has yet to be reported. Here yap1 and taz were found expressed in liver and other digestive organs in zebrafish embryos, and knockout of yap1 or taz did not lead to visible defects during embryogenesis. Interestingly, Taz was significantly increased in yap1 mutants, which may account for their normal development, albeit losing Yap1. However, yap1^−/−; taz^+/- embryos exhibited smaller digestive organs, and more than half of them showed bilateral livers and pancreas and non-looped intestines. Further analysis revealed that the disrupted gene function in yap1^−/−; taz^+/- embryos did not disturb liver bud formation, but instead impaired cell proliferation in liver and movement of the neighboring lateral plate mesoderm (LPM). Overexpression of wild type yap1 or taz could rescue the defective liver phenotypes in yap1^−/−; taz^+/- embryos, indicating that Yap1 cooperate with Taz to regulate the liver development. In addition, Yap1 was found to function in a Tead-dependent manner in the liver development. Our results suggest that Yap1/Taz regulate LPM movement and promote cell proliferation to ensure proper liver development in zebrafish.