Hippo signalling regulates Meox1 to control venous sprouting and lymphangiogenesis

The Hippo pathway, which regulates organ growth and cell fate control, is essential for lymphatic development. Nevertheless, the downstream target genes and mechanisms involved remain to be identified.

Here, by analysing yap1 mutant vasculature with single-cell genomics, we identify the homeobox transcription factor meox1 as a tissue-specific target of the Hippo pathway. Yap1 modulates meox1 expression through a conserved and functional upstream enhancer element in venous endothelial cells. Meox1 is indispensable for lymphatic development, acting both endothelial cell-autonomously and non-cell-autonomously.