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 Blood, 19 February 2009, Vol. 113, No. 8, pp. 1856-1859.
Prepublished online as a Blood First Edition Paper on September 24, 2008; DOI 10.1182/blood-2008-03-145789.

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VASCULAR BIOLOGY

Brief Report

Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic endothelial cell fate

Sunju Lee1, Jinjoo Kang1, Jaehyuk Yoo1, Sathish K. Ganesan1, Sarah C. Cook1, Berenice Aguilar1, Swapnika Ramu1, Juneyong Lee1, and Young-Kwon Hong1

1 Departments of Surgery and Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles

Specification of endothelial cell (EC) fate during vascular development is controlled by distinct key regulators. While Notch plays an essential role in induction of arterial phenotypes, COUP-TFII is required to maintain the venous EC identity. Homeodomain transcription factor Prox1 functions to reprogram venous ECs to lymphatic endothelial cells (LECs). Here, we report that the venous EC fate regulator COUP-TFII is expressed in LECs throughout development and physically interacts with Prox1 to form a stable complex in various cell types including LECs. We found that COUP-TFII functions as a coregulator of Prox1 to control several lineage-specific genes including VEGFR-3, FGFR-3, and neuropilin-1 and is required along with Prox1 to maintain LEC phenotype. Together, we propose that the physical and functional interactions of the 2 proteins constitute an essential part in the program specifying LEC fate and may provide the molecular basis for the hypothesis of venous EC identity being the prerequisite for LEC specification.


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