Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish

Cell Rep. 2015 Dec 1;13(9):1828-41. doi: 10.1016/j.celrep.2015.10.055. Epub 2015 Nov 19.

Abstract

Lymphatic vessels arise chiefly from preexisting embryonic veins. Genetic regulators of lymphatic fate are known, but how dynamic cellular changes contribute during the acquisition of lymphatic identity is not understood. We report the visualization of zebrafish lymphatic precursor cell dynamics during fate restriction. In the cardinal vein, cellular commitment is linked with the division of bipotential Prox1-positive precursor cells, which occurs immediately prior to sprouting angiogenesis. Following precursor division, identities are established asymmetrically in daughter cells; one daughter cell becomes lymphatic and progressively upregulates Prox1, and the other downregulates Prox1 and remains in the vein. Vegfc drives cell division and Prox1 expression in lymphatic daughter cells, coupling signaling dynamics with daughter cell fate restriction and precursor division.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Division
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Lymphangiogenesis / physiology
  • Lymphatic Vessels / cytology
  • Lymphatic Vessels / metabolism*
  • Microscopy, Confocal
  • Neovascularization, Physiologic
  • Signal Transduction
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / metabolism*
  • Zebrafish / growth & development
  • Zebrafish / metabolism*

Substances

  • Homeodomain Proteins
  • Tumor Suppressor Proteins
  • Vascular Endothelial Growth Factor C
  • prospero-related homeobox 1 protein