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The Hippo signaling pathway regulates many cellular processes, but has been specifically associated with control organ size and tumor growth. Yes-associated protein 1 (YAP1) is a transcriptional cofactor, in the Hippo pathway, that regulates gene expression when localized in the nucleus. Elevated expression of YAP1 in adult mouse liver leads to hepatomegaly and can cause hepatocellular carcinoma; while the loss of function studies reveal its importance in regulating cholangiocyte development. Here, we report the expression of YAP1 in mouse embryonic and postnatal hepatic cells, using AFP-GFP transgenic mice to identify the hepatocyte lineage. At embryonic day (E) 8.5, YAP1 is highly expressed in the endoderm, but is not present in the nucleus. Between E9.5–12.5, hepatic cells display low levels of nuclear and non-nuclear YAP1. The nuclear expression of YAP1 is first detected in a small subset of hepatic cells starting at E13.5 when the hepatoblasts begin to differentiate into hepatocytes and cholangiocytes. At E18.5, nuclear YAP1 is nearly undetectable in hepatoblasts and hepatocytes, but enriched within the nuclei of cholangiocytes. These levels remain similar postnatally, consistent with the role of YAP1 in cholangiocyte specification and maintenance. [ABSTRACT FROM AUTHOR]

Liver development is controlled by key signals and transcription factors that drive cell proliferation, migration, differentiation and functional maturation. In the adult liver, cell maturity can be perturbed by genetic and environmental factors that disrupt hepatic identity and function. Developmental signals and fetal genetic programmes are often dysregulated or reactivated, leading to dedifferentiation and disease. Here, we highlight signalling pathways and transcriptional regulators that drive liver cell development and primary liver cancers. We also discuss emerging models derived from pluripotent stem cells, 3D organoids and bioengineering for improved studies of signalling pathways in liver cancer and regenerative medicine. [ABSTRACT FROM AUTHOR]

Numerous laboratory and field studies have found that female Pacific salmon have higher mortality than males during their once-in-a-lifetime upriver spawning migration. However, the proximate cause(s) of this increased mortality are poorly understood. This study exposed sockeye salmon (Oncorhynchus nerka) to a mild capture and tagging stressor and evaluated physiological recovery and movement behaviour at 1 and 4 h postrelease. Female sockeye salmon did not expend more anaerobic energy in response to the stressor but did have higher plasma lactate levels 4 h after the stressor, indicating that females took longer to physiologically recover compared with males. In addition, female salmon had lower plasma glucose but higher plasma cortisol, plasma K+, and cardiac lactate levels compared with males. Male and female salmon had markedly different postrelease behaviours within the first hour of release; males were more likely to hold position within the staging area. Two potential mechanisms leading to increased mortality in female salmon were identified in this study: (a) prolonged recovery duration (possibly mediated by elevated plasma cortisol levels) and (b) insufficient oxygen delivery to the heart. [ABSTRACT FROM AUTHOR]