Article ; Online: The blood vasculature instructs lymphatic patterning in a SOX7-dependent manner.
2023 Volume 42, Issue 5, Page(s) e109032
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- ... ...
| 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. |
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| MeSH term(s) | Humans ; Mice ; Animals ; Endothelial Cells/metabolism ; Lymphatic Vessels/metabolism ; Gene Expression Regulation ; Endothelium, Vascular ; Transcription Factors/metabolism ; Lymphangiogenesis/genetics ; SOXF Transcription Factors/genetics ; SOXF Transcription Factors/metabolism | ||||||||||
| Chemical Substances | Transcription Factors ; SOX7 protein, human ; SOXF Transcription Factors ; Sox7 protein, mouse | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2023-01-30 | ||||||||||
| Publishing country | England | ||||||||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 586044-1 | ||||||||||
| ISSN | 1460-2075 ; 0261-4189 | ||||||||||
| ISSN (online) | 1460-2075 | ||||||||||
| ISSN | 0261-4189 | ||||||||||
| DOI | 10.15252/embj.2021109032 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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