1. Developmental Biology
  2. Stem Cells and Regenerative Medicine
Download icon

Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts

  1. Ruihua Ma
  2. Angelica Sofia Martínez-Ramírez
  3. Thomas L Borders
  4. Fanding Gao
  5. Beatriz Sosa-Pineda  Is a corresponding author
  1. Northwestern University Feinberg School of Medicine, United States
Research Article
  • Cited 0
  • Views 1,360
  • Annotations
Cite this article as: eLife 2020;9:e46206 doi: 10.7554/eLife.46206

Abstract

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.

Article and author information

Author details

  1. Ruihua Ma

    Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Angelica Sofia Martínez-Ramírez

    Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Thomas L Borders

    Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Fanding Gao

    Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Beatriz Sosa-Pineda

    Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States
    For correspondence
    beatriz.sosa-pineda@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6872-5444

Funding

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.

Ethics

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.

Reviewing Editor

  1. Holger Willenbring

Publication history

  1. Received: February 18, 2019
  2. Accepted: March 6, 2020
  3. Accepted Manuscript published: March 10, 2020 (version 1)
  4. Version of Record published: March 12, 2020 (version 2)

Copyright

© 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.

Metrics

  • 1,360
    Page views
  • 231
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    2. Genetics and Genomics
    Theodora Koromila et al.
    Research Article Updated

    Pioneer factors such as Zelda (Zld) help initiate zygotic transcription in Drosophila early embryos, but whether other factors support this dynamic process is unclear. Odd-paired (Opa), a zinc-finger transcription factor expressed at cellularization, controls the transition of genes from pair-rule to segmental patterns along the anterior-posterior axis. Finding that Opa also regulates expression through enhancer sog_Distal along the dorso-ventral axis, we hypothesized Opa’s role is more general. Chromatin-immunoprecipitation (ChIP-seq) confirmed its in vivo binding to sog_Distal but also identified widespread binding throughout the genome, comparable to Zld. Furthermore, chromatin assays (ATAC-seq) demonstrate that Opa, like Zld, influences chromatin accessibility genome-wide at cellularization, suggesting both are pioneer factors with common as well as distinct targets. Lastly, embryos lacking opa exhibit widespread, late patterning defects spanning both axes. Collectively, these data suggest Opa is a general timing factor and likely late-acting pioneer factor that drives a secondary wave of zygotic gene expression.

    1. Developmental Biology
    Laurent Jutras-Dubé et al.
    Research Article

    During development, cells gradually assume specialized fates via changes of transcriptional dynamics, sometimes even within the same developmental stage. For anterior-posterior (AP) patterning in metazoans, it has been suggested that the gradual transition from a dynamic genetic regime to a static one is encoded by different transcriptional modules. In that case, the static regime has an essential role in pattern formation in addition to its maintenance function. In this work, we introduce a geometric approach to study such transition. We exhibit two types of genetic regime transitions, respectively arising through local or global bifurcations. We find that the global bifurcation type is more generic, more robust, and better preserves dynamical information. This could parsimoniously explain common features of metazoan segmentation, such as changes of periods leading to waves of gene expressions, 'speed/frequency-gradient' dynamics, and changes of wave patterns. Geometric approaches appear as possible alternatives to gene regulatory networks to understand development.