Expression patterns of Yes-associated protein 1 in the developing mouse liver

Area of Science:

• Cell Biology
• Developmental Biology
• Molecular Biology

Background:

• The Hippo signaling pathway controls organ size and tumor growth.
• Yes-associated protein 1 (YAP1) is a transcriptional cofactor in this pathway, regulating gene expression upon nuclear localization.
• YAP1 dysregulation is linked to liver enlargement and cancer, and its role in cholangiocyte development is crucial.

Purpose of the Study:

• To investigate the expression pattern of YAP1 in mouse embryonic and postnatal hepatic cells.
• To identify the role of YAP1 in hepatocyte and cholangiocyte differentiation and maintenance.

Main Methods:

• Utilized AFP-GFP transgenic mice to trace hepatocyte lineage.
• Analyzed YAP1 expression levels (nuclear and non-nuclear) at various embryonic (E8.5-E18.5) and postnatal stages.
• Correlated YAP1 expression with hepatoblast differentiation into hepatocytes and cholangiocytes.

Main Results:

• YAP1 was highly expressed in the embryonic endoderm at E8.5 but lacked nuclear localization.
• Low levels of YAP1 were observed in hepatic cells between E9.5-12.5.
• Nuclear YAP1 first appeared in a subset of hepatic cells at E13.5 during differentiation.
• By E18.5 and postnatally, nuclear YAP1 was enriched in cholangiocytes, while nearly undetectable in hepatocytes.

Conclusions:

• YAP1 expression dynamics change significantly during liver development.
• Nuclear YAP1 enrichment in cholangiocytes suggests a critical role in their specification and maintenance.
• This study elucidates YAP1's specific function in the biliary lineage of the liver.