A novel transgenic reporter mouse strain for liver zonation study

Mature hepatocytes accomplish unique metabolic functions that are highly influenced by their specific position along the porto-central liver axis. The process that establishes complementary metabolic pathways within non-overlapping regions of the liver is called ‘liver zonation’. In recent years, canonical Wnt/beta-catenin signaling was identified as a major player in the establishment of hepatocyte zonation in the adult liver. On the other hand, much less is known about the pathways and mechanisms that establish liver zonation during development, or the role that non-parenchymal cells play in this process. Advancing this knowledge requires the identification of specific markers of ‘zonated’ hepatocytes and better tools to visualize the spatial segregation of ‘zonated’ hepatocytes over time. Our lab recently discovered that in Cldn2EGFP transgenic mice all hepatocytes expressing the green fluorescent reporter protein (GFP) localize around the perivenous (PV) area of the liver, whereas GFP+ hepatocytes and largely absent in periportal (PP) areas of the transgenic organ. By taking advantage of this unique valuable mouse model, I will: 1) examine how GFP+ hepatocytes allocate to specific liver compartments over time, as well as during hepatocyte regeneration following injury; 2) isolate pure populations of PV and PP hepatocytes using FACS to identify transcripts and gene pathways uniquely expressed in these populations; 3) investigate the potential involvement of macrophages and sinusoidal cells in early hepatocyte zonation.