The blood vasculature instructs lymphatics patterning in a SOX7 dependent manner
| Autor: | Davidson Tl, Emmanuelle Lesieur, Winnie Luu, Chiang Ikn, Friedemann Kiefer, Mehdi Moustaqil, Natasha L. Harvey, Mathias Francois, Arriola-Martinez L, Kari Alitalo, Kirschnick N, Jiang K, Renae Skoczylas, Kazenwadel J, Emma Sierecki, Kouskoff, Yann Gambin |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
government.form_of_government Growth factor medicine.medical_treatment Notch signaling pathway Repressor Biology Cell biology 03 medical and health sciences Lymphatic Endothelium 0302 clinical medicine Lymphatic system medicine.anatomical_structure Vascular endothelial growth factor C government medicine Lymphatic vessel Transcription factor 030217 neurology & neurosurgery 030304 developmental biology |
| Popis: | Despite a growing catalogue 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 lymphatic vessel patterning by modulating the transcription of lymphangiocrine signals. While SOX7 is not expressed in lymphatic endothelial cells (LECs), 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 signalling events crucial for lymphatic patterning, at least in part via the transcriptional repression of VEGFC levels in the blood vascular endothelium. |
| Databáze: | OpenAIRE |
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