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

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 BEC‐specific transcription factor, SOX7, plays a crucial role in a non‐cell‐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.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: The blood vasculature instructs lymphatic patterning in a SOX7‐dependent manner ; day:30 ; month:01 ; year:2023 ; extent:23 ; The EMBO journal / European Molecular Biology Organization ; (30.01.2023) (gesamt 23)

Beteiligte, Orts- und Zeitangaben

• Urheber: Chiang, Ivy K. N. ; Graus, Matthew S. ; Kirschnick, Nils ; Davidson, Tara ; Luu, Winnie ; Harwood, Richard ; Jiang, Keyi ; Li, Bitong ; Wong, Yew Yan ; Moustaqil, Mehdi ; Lesieur, Emmanuelle ; Skoczylas, Renae ; Kouskoff, Valerie ; Kazenwadel, Jan ; Arriola‐Martinez, Luis ; Sierecki, Emma ; Gambin, Yann ; Alitalo, Kari ; Kiefer, Friedmann ; Harvey, Natasha L. ; Francois, Mathias

Weitere Informationen

• DOI: 10.15252/embj.2021109032
• URN: urn:nbn:de:101:1-2023013014121531645390
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:33 MESZ