The blood vasculature instructs lymphatic patterning in a SOX7-dependent manner

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Date

2023

Authors

Chiang, I.K.N.
Graus, M.S.
Kirschnick, N.
Davidson, T.
Luu, W.
Harwood, R.
Jiang, K.
Li, B.
Wong, Y.Y.
Moustaqil, M.

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Journal article

Citation

EMBO Journal, 2023; 42(5):1-23

Statement of Responsibility

Ivy K N Chiang ... Natasha L Harvey ... et al.

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DOI

10.15252/embj.2021109032

Abstract

Despite a growing catalog of secreted factors critical for lymphatic network assembly, little is known about the mechanisms that modulate the expression level of these molecular cues in blood vascular endothelial cells (BECs). Here, we show that a BECspecific transcription factor, SOX7, plays a crucial role in a noncell-autonomous manner by modulating the transcription of angiocrine signals to pattern lymphatic vessels. While SOX7 is not expressed in lymphatic endothelial cells (LECs), the conditional loss of SOX7 function in mouse embryos causes a dysmorphic dermal lymphatic phenotype. We identify novel distant regulatory regions in mice and humans that contribute to directly repressing the transcription of a major lymphangiogenic growth factor (Vegfc) in a SOX7-dependent manner. Further, we show that SOX7 directly binds HEY1, a canonical repressor of the Notch pathway, suggesting that transcriptional repression may also be modulated by the recruitment of this protein partner at Vegfc genomic regulatory regions. Our work unveils a role for SOX7 in modulating downstream signaling events crucial for lymphatic patterning, at least in part via the transcriptional repression of VEGFC levels in the blood vascular endothelium.

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Data source: Data availability, https://doi.org/10.15252/embj.2021109032

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2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license

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Grant ID

http://purl.org/au-research/grants/nhmrc/116400
 http://purl.org/au-research/grants/arc/DP200100250
 http://purl.org/au-research/grants/nhmrc/1111169
 http://purl.org/au-research/grants/nhmrc/1107643
 http://purl.org/au-research/grants/nhmrc/1107643
 http://purl.org/au-research/grants/nhmrc/1111169
 http://purl.org/au-research/grants/nhmrc/116400

Published Version

https://doi.org/10.15252/embj.2021109032

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Persistent link to this record

https://hdl.handle.net/2440/137530