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Polarisation in the liver

Despite the inherent ability of the liver to regenerate itself, liver failure constitutes a significant health problem worldwide. There is an imminent need to understand the mechanisms guiding liver regeneration and function.
Polarisation in the liver
Many biological processes including development and tissue function are asymmetric and rely on cell polarity. Generation of cell polarity involves the establishment of distinct cellular membrane domains – apical and basolateral, separated by tight junctions and adherens junctions.

The distinct microarchitecture of the liver relies on the correct polarisation of hepatocytes and cholangiocytes, which line the bile duct. Hepatocytes and cholangiocytes emerge from a common precursor cell called hepatoblast indicating that the molecular machinery to generate the two different types of polarity is fundamentally the same. This suggests that the polarised morphology results from alterations in the activation of specific key pathways to inner or outer cues.

Liver polarisation is an essential component for bile secretion and overall liver function. Scientists of the EU-funded LIVER (Role of actin-based contraction and scaffolding in hepatocyte polarization, generation of liver-specific microarchitecture and liver tissue functioning) project set out to investigate the molecular principles underlying the polarisation of hepatocytes. They focused on the role of the actin machinery in shaping the apical region as actin filaments are enriched at the cell cortex underneath the apical plasma membrane in polarised cells.

Results showed that myosin contractility and mechanical tension were not responsible for hepatocyte polarity. To identify the key molecular pathways involved in the shaping of the hepatocyte apical domain, scientists performed RNA deep sequencing. Several pathways of interest were highlighted that could be exploited in further studies.

For visualisation of the underlying mechanism of polarity, researchers performed structured illumination microscopy. They observed that the actin filaments in hepatocytic polarity were long, interconnected and displayed a different orientation.

Collectively, the findings of the study indicated that regulation of the actin severing and capping pathways could be responsible for the formation of distinct polarity states. Further testing on in vivo liver models will be required to validate this hypothesis.

Related information

Keywords

Cell polarity, hepatocytes, apical domain, LIVER, actin
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