Yap1/Taz are essential for the liver development in zebrafish

Area of Science:

• Developmental Biology
• Cell Biology
• Genetics

Background:

• The Hippo pathway is a critical regulator of organ size.
• Yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) are key downstream effectors of the Hippo pathway.
• The role of Yap/Taz in embryonic liver development remains largely unexplored.

Purpose of the Study:

• To investigate the function of Yap1 and Taz in embryonic liver development using zebrafish as a model.
• To elucidate the molecular mechanisms by which Yap1/Taz regulate liver organogenesis.

Main Methods:

• Zebrafish embryo generation with targeted knockout of yap1 and taz genes.
• Phenotypic analysis of digestive organ development in mutant embryos.
• Gene expression analysis and rescue experiments using wild-type yap1 and taz overexpression.

Main Results:

• While individual knockout of yap1 or taz did not cause defects, combined yap1 deficiency and partial taz loss (yap1-/-; taz+/-) resulted in smaller digestive organs, including bilateral livers and pancreas, and non-looped intestines.
• These defects were linked to impaired liver cell proliferation and disrupted lateral plate mesoderm (LPM) movement, not initial liver bud formation.
• Overexpression of wild-type yap1 or taz rescued the observed liver phenotypes, confirming their cooperative role.
• Yap1 was found to function in a Tead-dependent manner in liver development.

Conclusions:

• Yap1 and Taz act cooperatively to regulate embryonic liver development in zebrafish.
• Yap1/Taz signaling is essential for promoting cell proliferation and coordinating LPM movement during liver organogenesis.
• These findings highlight the conserved role of the Hippo pathway effectors in vertebrate organ development.