@article{RenzOttenFaurobertetal.2015,
  author    = {Renz, Marc and Otten, Cecile and Faurobert, Eva and Rudolph, Franziska and Zhu, Yuan and Boulday, Gwenola and Duchene, Johan and Mickoleit, Michaela and Dietrich, Ann-Christin and Ramspacher, Caroline and Steed, Emily and Manet-Dupe, Sandra and Benz, Alexander and Hassel, David and Vermot, Julien and Huisken, Jan and Tournier-Lasserve, Elisabeth and Felbor, Ute and Sure, Ulrich and Albiges-Rizo, Corinne and Abdelilah-Seyfried, Salim},
  title     = {Regulation of beta 1 Integrin-Klf2-Mediated angiogenesis by CCM proteins},
  series = {Developmental cell},
  volume    = {32},
  journal   = {Developmental cell},
  number    = {2},
  publisher = {Cell Press},
  address   = {Cambridge},
  issn      = {1534-5807},
  doi       = {10.1016/j.devcel.2014.12.016},
  pages     = {181 -- 190},
  year      = {2015},
  abstract  = {Mechanotransduction pathways are activated in response to biophysical stimuli during the development or homeostasis of organs and tissues. In zebrafish, the blood-flow-sensitive transcription factor Klf2a promotes VEGF-dependent angiogenesis. However, the means by which the Klf2a mechanotransduction pathway is regulated to prevent continuous angiogenesis remain unknown. Here we report that the upregulation of klf2 mRNA causes enhanced egfl7 expression and angiogenesis signaling, which underlies cardiovascular defects associated with the loss of cerebral cavernous malformation (CCM) proteins in the zebrafish embryo. Using CCM-protein-depleted human umbilical vein endothelial cells, we show that the misexpression of KLF2 mRNA requires the extracellular matrix-binding receptor beta 1 integrin and occurs in the absence of blood flow. Downregulation of beta 1 integrin rescues ccm mutant cardiovascular malformations in zebrafish. Our work reveals a beta 1 integrin-Klf2-Egfl7-signaling pathway that is tightly regulated by CCM proteins. This regulation prevents angiogenic overgrowth and ensures the quiescence of endothelial cells.},
  language  = {en}
}
@article{DonatLourencoPaolinietal.2018,
  author    = {Donat, Stefan and Lourenco, Marta Sofia Rocha and Paolini, Alessio and Otten, Cecile and Renz, Marc and Abdelilah-Seyfried, Salim},
  title     = {Heg1 and Ccm1/2 proteins control endocardial mechanosensitivity during zebrafish valvulogenesis},
  series = {eLife},
  volume    = {7},
  journal   = {eLife},
  publisher = {eLife Sciences Publications},
  address   = {Cambridge},
  issn      = {2050-084X},
  doi       = {10.7554/eLife.28939},
  pages     = {22},
  year      = {2018},
  abstract  = {Endothelial cells respond to different levels of fluid shear stress through adaptations of their mechanosensitivity. Currently, we lack a good understanding of how this contributes to sculpting of the cardiovascular system. Cerebral cavernous malformation (CCM) is an inherited vascular disease that occurs when a second somatic mutation causes a loss of CCM1/KRIT1, CCM2, or CCM3 proteins. Here, we demonstrate that zebrafish Krit1 regulates the formation of cardiac valves. Expression of heg1, which encodes a binding partner of Krit1, is positively regulated by blood-flow. In turn, Heg1 stabilizes levels of Krit1 protein, and both Heg1 and Krit1 dampen expression levels of klf2a, a major mechanosensitive gene. Conversely, loss of Krit1 results in increased expression of klf2a and notch1b throughout the endocardium and prevents cardiac valve leaflet formation. Hence, the correct balance of blood-flow-dependent induction and Krit1 protein mediated repression of klf2a and notch1b ultimately shapes cardiac valve leaflet morphology.},
  language  = {en}
}