PUBLICATION

Proper migration of lymphatic endothelial cells requires survival and guidance cues from arterial mural cells

Authors
Peng, D., Ando, K., Hußmann, M., Gloger, M., Skoczylas, R., Mochizuki, N., Betsholtz, C., Fukuhara, S., Schulte-Merker, S., Lawson, N.D., Koltowska, K.
ID
ZDB-PUB-220323-40
Date
2022
Source
eLIFE   11: (Journal)
Registered Authors
Ando, Koji, Betsholtz, Christer, Fukuhara, Shigetomo, Lawson, Nathan, Mochizuki, Naoki, Schulte-Merker, Stefan
Keywords
developmental biology, zebrafish
MeSH Terms
  • Animals
  • Arteries
  • Cues
  • Endothelial Cells*/physiology
  • Vascular Endothelial Growth Factor C*/physiology
  • Zebrafish
PubMed
35316177 Full text @ Elife
Abstract
The migration of lymphatic endothelial cells (LECs) is key for the development of the complex and vast lymphatic vascular network that pervades most tissues in an organism. In zebrafish, arterial intersegmental vessels together with chemokines have been shown to promote lymphatic cell migration from the horizontal myoseptum (HM). We observed that emergence of mural cells around the intersegmental arteries coincides with lymphatic departure from HM which raised the possibility that arterial mural cells promote LEC migration. Our live imaging and cell ablation experiments revealed that LECs migrate slower and fail to establish the lymphatic vascular network in the absence of arterial mural cells. We determined that mural cells are a source for the C-X-C motif chemokine 12 (Cxcl12a and Cxcl12b), Vascular endothelial growth factor C (Vegfc) and Collagen and calcium-binding EGF domain-containing protein 1 (Ccbe1). We showed that chemokine and growth factor signalling function cooperatively to induce robust LEC migration. Specifically, Vegfc-Vegfr3 signalling, but not chemokines, induces extracellular signal-regulated kinase (ERK) activation in LECs, and has an additional pro-survival role in LECs during the migration. Together, the identification of mural cells as a source for signals that guide LEC migration and survival will be important in the future design for rebuilding lymphatic vessels in disease contexts.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes