PUBLICATION

Live imaging reveals a conserved role of fatty acid β-oxidation in early lymphatic development in zebrafish

Authors
Zecchin, A., Wong, B., Tembuyser, B., Souffreau, J., Van Nuffelen, A., Wyns, S., Vinckier, S., Carmeliet, P., Dewerchin, M.
ID
ZDB-PUB-180509-9
Date
2018
Source
Biochemical and Biophysical Research Communications   503(1): 26-31 (Journal)
Registered Authors
Keywords
CPT1A, Danio rerio, Fatty acid oxidation, Lymphangiogenesis, Lymphatic development, Zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Carnitine O-Palmitoyltransferase/antagonists & inhibitors
  • Carnitine O-Palmitoyltransferase/genetics
  • Carnitine O-Palmitoyltransferase/metabolism
  • Cell Differentiation
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism
  • Fatty Acids/metabolism*
  • Gene Targeting
  • Lymphangiogenesis/genetics
  • Lymphangiogenesis/physiology
  • Lymphatic Vessels/embryology*
  • Lymphatic Vessels/metabolism*
  • Models, Animal
  • Oxidation-Reduction
  • Time-Lapse Imaging
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
29730294 Full text @ Biochem. Biophys. Res. Commun.
Abstract
During embryonic development, lymphatic endothelial cells (LECs) differentiate from venous endothelial cells (VECs), a process that is tightly regulated by several genetic signals. While the aquatic zebrafish model is regularly used for studying lymphangiogenesis and offers the unique advantage of time-lapse video-imaging of lymphatic development, some aspects of lymphatic development in this model differ from those in the mouse. It therefore remained to be determined whether fatty acid β-oxidation (FAO), which we showed to regulate lymphatic formation in the mouse, also co-determines lymphatic development in this aquatic model. Here, we took advantage of the power of the zebrafish embryo model to visualize the earliest steps of lymphatic development through time-lapse video-imaging. By targeting zebrafish isoforms of carnitine palmitoyltransferase 1a (Cpt1a), a rate controlling enzyme of FAO, with multiple morpholinos, we demonstrate that reducing CPT1A levels and FAO flux during zebrafish development impairs lymphangiogenic secondary sprouting, the initiation of lymphatic development in the zebrafish trunk, and the formation of the first lymphatic structures. These findings not only show evolutionary conservation of the importance of FAO for lymphatic development, but also suggest a role for FAO in co-regulating the process of VEC-to-LEC differentiation in zebrafish in vivo.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping