GATA2 participates in the recanalization of lymphatic vessels after surgical lymph node extirpation

Abstract

Lymphatic recanalization failure after lymphadenectomy constitutes a major risk of lymphedema in cancer surgery. It has been reported that GATA2, a zinc finger transcription factor, is expressed in lymphatic endothelial cells and is involved in the development of fetal lymphatic vessels. GATA3, another member of the GATA family of transcription factors, is required for the differentiation of lymphoid tissue inducer (LTi) cells and is essential for lymph node formation. However, how GATA2 and GATA3 function in recanalization after the surgical extirpation of lymphatic vessels has not been elucidated. Employing a new model of lymphatic recanalization, we examined the lymphatic reconnection process in Gata2 heterozygous deficient (Gata2^+/- ) and Gata3 heterozygous deficient (Gata3^+/- ) mice. We found that lymphatic recanalization was significantly impaired in Gata2^+/- mice, while Gata3^+/- mice rarely showed such abnormalities. Notably, the perturbed lymphatic recanalization in the Gata2^+/- mice was partially restored by crossing with the Gata3^+/- mice. Our results demonstrate for the first time that GATA2 participates in the regeneration of damaged lymphatic vessels and the unexpected suppressive activity of GATA3 against lymphatic recanalization processes.

Keywords: Gata2; Gata3; haploinsufficiency; lymphatic vessels; recanalization.