Authors:
Dieterich LC, Klein S, Mathelier A, Sliwa-Primorac A, Ma Q, Hong YK,... Lassmann, T., et al.
Authors notes:
Cell Rep. 2015;13(7):1493-504.
Keywords:
lymphangiogenesis, MAFB, VEGF-C, PROX1, lymphatic patterning, skin, lymphatic progenitor cells, target gene expression, cap analysis of gene expression; CAGE, RNA sequencing, transcription factors, VEGFR-3
Abstract:
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 lymphatic endothelial cells and to identify the transcription factors involved.
We found that MAFB, a transcription factor involved in differentiation of various cell types, is rapidly induced and activated by VEGF-C.
MAFB induced expression of PROX1 as well as other transcription factors and markers of differentiated lymphatic endothelial cells, indicating a role in the maintenance of the mature lymphatic endothelial cell phenotype.
Correspondingly, E14.5 Mafb-/- embryos showed impaired lymphatic patterning in the skin.
This suggests that MAFB is an important transcription factor involved in lymphangiogenesis.