HHEX is a transcriptional regulator of the VEGFC/FLT4/PROX1 signaling axis during vascular development.

Nature Communications
Sébastien GauvritDidier Yr Stainier

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.

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Nov 30, 2019·Cancers·Stefan Nagel, Hans G Drexler
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Datasets Mentioned

BETA
GSE111963

Methods Mentioned

BETA
transgenic
PCR
immunoprecipitation
genotyping
ChIP
RNA-Seq

Software Mentioned

Ensemble
featureCounts
DESeq2
ZEN
GraphPad
Subread package
STAR
ImageJ
Reaper
Ensembl

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