PUBLICATION

Vasohibin-1 selectively regulates secondary sprouting and lymphangiogenesis in the zebrafish trunk

Authors
Bastos de Oliveira, M., Meier, K., Jung, S., Bartels-Klein, E., Coxam, B., Geudens, I., Szymborska, A., Skoczylas, R., Fechner, I., Koltowska, K., Gerhardt, H.
ID
ZDB-PUB-210207-16
Date
2021
Source
Development (Cambridge, England)   148(4): (Journal)
Registered Authors
Fechner, Ines, Gerhardt, Holger, Meier, Katja, Szymborska-Mell, Anna
Keywords
Lymphangiogenesis, Microtubules, Sprouting angiogenesis, Tubulin detyrosination, Vasohibin-1
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Cell Cycle Proteins/chemistry
  • Cell Cycle Proteins/genetics*
  • Cell Cycle Proteins/metabolism
  • Conserved Sequence
  • Embryonic Development/genetics*
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental
  • Immunohistochemistry
  • Lymphangiogenesis/genetics*
  • Microtubules/metabolism
  • Models, Biological
  • Zebrafish/embryology*
  • Zebrafish/genetics*
PubMed
33547133 Full text @ Development
Abstract
Previous studies have shown that Vasohibin-1 (Vash1) is stimulated by VEGFs in endothelial cells and that its overexpression interferes with angiogenesis in vivo Recently, Vash1 was found to mediate tubulin detyrosination, a post-translational modification that is implicated in many cell functions, such as cell division. Here we used the zebrafish embryo to investigate the cellular and subcellular mechanisms of Vash1 on endothelial microtubules during formation of the trunk vasculature. We show that microtubules within venous-derived secondary sprouts are strongly and selectively detyrosinated in comparison with other endothelial cells, and that this difference is lost upon vash1 knockdown. Vash1 depletion in zebrafish specifically affected secondary sprouting from the posterior cardinal vein, increasing endothelial cell divisions and cell number in the sprouts. We show that altering secondary sprout numbers and structure upon Vash1 depletion leads to defective lymphatic vessel formation and ectopic lymphatic progenitor specification in the zebrafish trunk.
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