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

Area of Science:

• Endothelial cell biology
• Vascular development
• Molecular genetics

Background:

• Lymphatic network assembly relies on secreted factors, but their regulation in blood vascular endothelial cells (BECs) is poorly understood.
• The mechanisms controlling the expression of molecular cues for lymphatic patterning remain largely unknown.

Purpose of the Study:

• To investigate the role of BEC-specific transcription factors in non-cell-autonomous patterning of lymphatic vessels.
• To identify novel regulatory mechanisms controlling lymphangiogenic growth factor expression in BECs.

Main Methods:

• Conditional loss-of-function studies in mouse embryos.
• Identification of distant regulatory regions in mice and humans.
• Analysis of SOX7 binding to HEY1 and genomic regulatory regions.

Main Results:

• Conditional loss of SOX7 in BECs leads to dysmorphic dermal lymphatic vasculature.
• SOX7 represses the transcription of Vascular Endothelial Growth Factor C (Vegfc) via distant regulatory elements.
• SOX7 directly interacts with HEY1, a Notch pathway repressor, at Vegfc regulatory regions.

Conclusions:

• SOX7, a BEC-specific transcription factor, is essential for lymphatic vessel patterning.
• SOX7 modulates lymphangiogenesis through transcriptional repression of Vegfc in BECs.
• This study uncovers a novel mechanism involving SOX7 and HEY1 in regulating angiocrine signals for lymphatic development.