期刊
CELL REPORTS
卷 13, 期 7, 页码 1493-1504出版社
CELL PRESS
DOI: 10.1016/j.celrep.2015.10.002
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资金
- Swiss National Science Foundation [310030B_147087]
- European Research Council Grant LYVICAM
- Oncosuisse
- Krebsliga Zurich
- Leducq Foundation Transatlantic Network of Excellence Grant Lymph Vessels in Obesity and Cardiovascular Disease [11CVD03]
- Genome Canada Large-Scale Applied Research Grant [174CDE]
- BC Children's Hospital Foundation
- Child and Family Research Institute, Vancouver, Canada
- MEXT
- MEXT, Japan
VEGF-C/VEGFR-3 signaling plays a central role in lymphatic development, regulating the budding of lymphatic progenitor cells from embryonic veins and maintaining the expression of PROX1 during later developmental stages. However, how VEGFR-3 activation translates into target gene expression is still not completely understood. We used cap analysis of gene expression (CAGE) RNA sequencing to characterize the transcriptional changes invoked by VEGF-C in LECs and to identify the transcription factors (TFs) involved. We found that MAFB, a TF involved in differentiation of various cell types, is rapidly induced and activated by VEGF-C. MAFB induced expression of PROX1 as well as other TFs and markers of differentiated LECs, indicating a role in the maintenance of the mature LEC phenotype. Correspondingly, E14.5 Mafb(-/-) embryos showed impaired lymphatic patterning in the skin. This suggests that MAFB is an important TF involved in lymphangiogenesis.
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