Submitted March 24, 2008
Accepted August 31, 2008
Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic endothelial cell fate
Sunju Lee, Jinjoo Kang, Jaehyuk Yoo, Sathish Kumar Ganesan, Sarah C. Cook, Berenice Aguilar, Swapnika Ramu, Juneyong Lee, and Young-Kwon Hong*
Departments of Surgery and of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
* Corresponding author; email: young.hong{at}usc.edu.
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 interaction of the two proteins constitutes 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.
