TRANSCRIPTION FACTOR FOXC2 DEMARCATES THE JUGULAR LYMPHANGIOGENIC REGION IN AVIAN EMBRYOS

Abstract

In the human, mutations of the forkheadwinged-helix transcription factor FOXC2cause the lymphedema-distichiasis syndrome,which is characterized by a double row ofeyelashes and pubertal onset lymphedema ofthe legs due to hyperplasia and malformationof lymphatic collectors. While a function ofFOXC2 for the differentiation of lymphaticcollectors is well documented, recent studieshave indicated an early function for thesprouting of lymphatics from embryonic veins.We studied the expression of FoxC2 in earlyavian embryos and compared its expressionpattern with that of the homeobox transcriptionfactor Prox1, which is essential forlymphatic endothelial cell (LEC) development.We show that FoxC2 demarcates a segmentof the somatopleura in the cervical region onembryonic day (ED) 3, before Prox1 isexpressed. On ED 4, its expression domaincoincides with that of Prox1 in the jugularregion. This region is characterized by theconfluence of Tie2-positive anterior andposterior cardinal veins. It has been shownthat Prox1 expression in a subpopulation ofvenous endothelial cells induces transdifferentiationinto LECs. Our data suggest thatFoxC2, in addition to its late functions duringlymph collector differentiation, has an earlyfunction during lymphendothelial commitmentof venous ECs in the jugular region.