PROX1

PROX1, also known as Prospero homeobox protein 1, is a transcription factor encoded by the PROX1 gene in humans. It belongs to the homeobox-containing family and functions as a key regulator of cell fate decisions during development and in adult tissues.

In development, PROX1 is best known as a master regulator of lymphatic endothelial cell identity and lymphangiogenesis. It is induced in venous endothelium by SOX18 and promotes the lymphatic gene program, including the expression of lymphatic markers such as VEGFR-3 (FLT4). PROX1 helps maintain lymphatic endothelial cell identity by repressing blood vascular gene programs, enabling proper formation and sprouting of the lymphatic vasculature. Loss or alteration of PROX1 in animal models leads to defects in lymphatic development and related fluid drainage, highlighting its essential role in this process.

PROX1 also contributes to development outside the lymphatic system. In the brain, it participates in the development and maturation of the dentate gyrus and granule neurons, and it has a role in adult neurogenesis. It is expressed in several other tissues, where it participates in lineage specification and cellular differentiation programs, demonstrating context-dependent functions beyond its lymphatic roles.

Mechanistically, PROX1 acts as a transcription factor by binding DNA via its homeodomain and regulating networks of target genes. Its activity is integrated with signaling pathways such as VEGF-C/VEGFR-3 and interacts with other transcriptional regulators to orchestrate tissue-specific programs.

Clinical significance of PROX1 includes associations with developmental lymphatic disorders and with cancer progression in which lymphangiogenesis can influence metastasis. It remains a focus of research as a potential biomarker and therapeutic target in diseases involving lymphatic vessels and related tissues.