The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells

R. Sathish Srinivasan, Xin Geng, Ying Yang, Yingdi Wang, Suraj Mukatira, Michèle Studer, Marianna P R Porto, Oleg Lagutin, Guillermo Oliver*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

157 Scopus citations

Abstract

The homeobox gene Prox1 is crucial for mammalian lymphatic vascular development. In the absence of Prox1, lymphatic endothelial cells (LECs) are not specified. The maintenance of LEC identity also requires the constant expression of Froxl. However, the mechanisms controlling the expression of this gene in LECs remain poorly understood. The SRY-related gene Sox18 is required to induce Prox1 expression in venous LEC progenitors. Although Sox18 is also expressed in embryonic arteries, these vessels do not express Prox1, nor do they give rise to LECs. This finding suggests that some venous endothelial cell-specific factor is required for the activation of Prox1. Here we demonstrate that the nuclear hormone receptor Coup-TFII is necessary for the activation of Prox1 in embryonic veins by directly binding a conserved DNA domain in the regulatory region of Prox1. In addition, we show that the direct interaction between nuclear hormone receptors and Prox1 is also necessary for the maintenance of Prox1 expression during early stages of LEC specification and differentiation.

Original languageEnglish (US)
Pages (from-to)696-707
Number of pages12
JournalGenes and Development
Volume24
Issue number7
DOIs
StatePublished - Apr 1 2010

Keywords

  • Coup-tfii
  • Endothelial cell
  • Lymphatics
  • Mouse
  • Prox1

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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