Hippo signalling regulates transitory Meox1 control of venous cell adhesion and sprouting during lymphatic vascular development [snATAC-Seq]

ABSTRACT: During vertebrate development, the lymphatic vasculature first emerges by cellular sprouting from pre-existing embryonic veins. A small number of lymphatic progenitors sprout out from the walls of functional blood vessels and invade growing tissues to generate an entirely new vasculature. The regulation of this process at a cellular and molecular level, remains to be fully understood. The Hippo pathway, which controls organ growth and morphogenesis, has been recently identified as a major new regulator of lymphatic development. The downstream molecular and cellular effectors by which Hippo signalling acts are unknown. Here, we exploit the conserved nature of lymphatic development in zebrafish. Single-cell RNA and single-nuclei ATAC-sequencing of vasculature in yap1 mutants identified the homeobox transcription factor meox1 as an unexpected, tissue-specific target. Yap1 controls meox1 expression directly through a conserved and functional upstream enhancer element. Meox1 is indispensable for lymphatic development, acting both endothelial cell-autonomously and non-autonomously. While in other contexts Meox1 regulates cell-cycle progression, here, Meox1 is essential for normal cell sprouting from veins and acts in a temporally restricted and vessel-specific manner, controlling cell adhesion and sprout elongation. This identifies a unique function for Meox1 and uncovers a paradigm by which a tissue-specific effector of the Hippo pathway controls the emergence of a new vascular network.

ORGANISM(S): Danio rerio

PROVIDER: GSE255821 | GEO | 2026/09/24

REPOSITORIES: GEO