Axon guidance genes control hepatic artery development

Lila Gannoun, Catalina De Schrevel, Morgane Belle, Nicolas Dauguet, Younes Achouri, Axelle Loriot, Christophe Vanderaa, Sabine Cordi, Alexandra Dili, Yves Heremans, Ilse Rooman, Isabelle A Leclercq, Patrick Jacquemin, Laurent Gatto, Frédéric P Lemaigre

Research output: Contribution to journalArticlepeer-review

Abstract

Earlier data on liver development demonstrated that morphogenesis of the bile duct, portal mesenchyme and hepatic artery is interdependent, yet how this interdependency is orchestrated remains unknown. Here, using 2D and 3D imaging, we first describe how portal mesenchymal cells become organised to form hepatic arteries. Next, we examined intercellular signalling active during portal area development and found that axon guidance genes are dynamically expressed in developing bile ducts and portal mesenchyme. Using tissue-specific gene inactivation in mice, we show that the repulsive guidance molecule BMP co-receptor A (RGMA)/neogenin (NEO1) receptor/ligand pair is dispensable for portal area development, but that deficient roundabout 2 (ROBO2)/SLIT2 signalling in the portal mesenchyme causes reduced maturation of the vascular smooth muscle cells that form the tunica media of the hepatic artery. This arterial anomaly does not impact liver function in homeostatic conditions, but is associated with significant tissular damage following partial hepatectomy. In conclusion, our work identifies new players in development of the liver vasculature in health and liver regeneration.

Original languageEnglish
Article numberdev201642
Number of pages15
JournalDevelopment
Volume150
Issue number16
DOIs
Publication statusPublished - 15 Aug 2023

Bibliographical note

© 2023. Published by The Company of Biologists Ltd.

Keywords

  • Liver development
  • Slit-Robo signalling
  • Liver mesenchyme

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