Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts
The distribution of complementary metabolic functions in hepatocytes along a portocentral axis is called liver zonation. Endothelial secreted Wnt ligands maintain metabolic zonation in the adult murine liver but whether those ligands are necessary to initiate zonation in the immature liver has been only partially explored. Also, numerous non-metabolic proteins display zonated expression in the adult liver but it is not entirely clear if their localization requires endothelial Wnts. Here we used a novel transgenic mouse model to compare the spatial distribution of zonated non-metabolic proteins with that of typical zonated metabolic enzymes during liver maturation and after acute injury induced by carbon tetrachloride (CCl4). We also investigated how preventing Wnt ligand secretion from endothelial cells affects zonation patterns under homeostasis and after acute injury. Our study demonstrates that metabolic and non-metabolic zonation are established non-synchronously during maturation and regeneration and require multiple endothelial Wnt sources.
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 - 7.
Article and author information
Feinberg School of Medicine (New Faculty Award 10040043-01)
- Beatriz Sosa-Pineda
Consejo Nacional de Ciencia y Tecnología (Postdoctoral Fellowship (ASMR))
- Angelica Sofia Martínez-Ramírez
Feinberg School of Medicine funded all the experiments associated with the study.CONACYT awarded a fellowship to Dr. Martinez-RamirezThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (IS00003824, welfare assurance number A3283-01) of Northwestern University.
- Holger Willenbring
- Received: February 18, 2019
- Accepted: March 6, 2020
- Accepted Manuscript published: March 10, 2020 (version 1)
- Version of Record published: March 12, 2020 (version 2)
© 2020, Ma et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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