HHEX is a Transcriptional Regulator of the VEGFC/FLT4/PROX1 Signaling Axis During Vascular Development

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jul 15

PMID 30006544

Citations 40

Authors

Sebastien Gauvrit

Alethia Villasenor

Boris Strilic

Philip Kitchen

Michelle M Collins

Ruben Marin-Juez

Stefan Guenther

Hans-Martin Maischein

Nana Fukuda

Maurice A Canham

Joshua M Brickman

Clifford W Bogue

Padma-Sheela Jayaraman

Didier Y R Stainier

Affiliations

Soon will be listed here.

Abstract

Formation of the lymphatic system requires the coordinated expression of several key regulators: vascular endothelial growth factor C (VEGFC), its receptor FLT4, and a key transcriptional effector, PROX1. Yet, how expression of these signaling components is regulated remains poorly understood. Here, using a combination of genetic and molecular approaches, we identify the transcription factor hematopoietically expressed homeobox (HHEX) as an upstream regulator of VEGFC, FLT4, and PROX1 during angiogenic sprouting and lymphatic formation in vertebrates. By analyzing zebrafish mutants, we found that hhex is necessary for sprouting angiogenesis from the posterior cardinal vein, a process required for lymphangiogenesis. Furthermore, studies of mammalian HHEX using tissue-specific genetic deletions in mouse and knockdowns in cultured human endothelial cells reveal its highly conserved function during vascular and lymphatic development. Our findings that HHEX is essential for the regulation of the VEGFC/FLT4/PROX1 axis provide insights into the molecular regulation of lymphangiogenesis.

Citing Articles

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