@article{RoedelOttenDonatetal.2019,
  author    = {R{\"o}del, Claudia Jasmin and Otten, Cecile and Donat, Stefan and Louren{\c{c}}o, Marta Sofia Rocha and Fischer, Dorothea and Kuropka, Benno and Paolini, Alessio and Freund, Christian and Abdelilah-Seyfried, Salim},
  title     = {Blood Flow Suppresses Vascular Anomalies in a Zebrafish Model of Cerebral Cavernous Malformations},
  series = {Circulation Research},
  volume    = {125},
  journal   = {Circulation Research},
  number    = {10},
  publisher = {Lippincott Williams \& Wilkins},
  address   = {Philadelphia},
  issn      = {0009-7330},
  doi       = {10.1161/CIRCRESAHA.119.315076},
  pages     = {E43 -- E54},
  year      = {2019},
  abstract  = {RATIONALE: Pathological biomechanical signaling induces vascular anomalies including cerebral cavernous malformations (CCM), which are caused by a clonal loss of CCM1/KRIT1 (Krev interaction trapped protein 1), CCM2/MGC4607, or CCM3/PDCD10. Why patients typically experience lesions only in lowly perfused venous capillaries of the cerebrovasculature is completely unknown. OBJECTIVE: In contrast, animal models with a complete loss of CCM proteins lack a functional heart and blood flow and exhibit vascular anomalies within major blood vessels as well. This finding raises the possibility that hemodynamics may play a role in the context of this vascular pathology. METHODS AND RESULTS: Here, we used a genetic approach to restore cardiac function and blood flow in a zebrafish model of CCM1. We find that blood flow prevents cardiovascular anomalies including a hyperplastic expansion within a large Ccm1-deficient vascular bed, the lateral dorsal aorta. CONCLUSIONS: This study identifies blood flow as an important physiological factor that is protective in the cause of this devastating vascular pathology.},
  language  = {en}
}
@misc{MerksSwinarskiMeyeretal.2018,
  author    = {Merks, Anne Margarete and Swinarski, Marie and Meyer, Alexander Matthias and M{\"u}ller, Nicola Victoria and {\"O}zcan, Ismail and Donat, Stefan and Burger, Alexa and Gilbert, Stephen and Mosimann, Christian and Abdelilah-Seyfried, Salim and Pan{\´a}kov{\´a}, Daniela},
  title     = {Planar cell polarity signalling coordinates heart tube remodelling through tissue-scale polarisation of actomyosin activity},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe},
  number    = {849},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-42702},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-427026},
  pages     = {17},
  year      = {2018},
  abstract  = {Development of a multiple-chambered heart from the linear heart tube is inherently linked to cardiac looping. Although many molecular factors regulating the process of cardiac chamber ballooning have been identified, the cellular mechanisms underlying the chamber formation remain unclear. Here, we demonstrate that cardiac chambers remodel by cell neighbour exchange of cardiomyocytes guided by the planar cell polarity (PCP) pathway triggered by two non-canonical Wnt ligands, Wnt5b and Wnt11. We find that PCP signalling coordinates the localisation of actomyosin activity, and thus the efficiency of cell neighbour exchange. On a tissue-scale, PCP signalling planar-polarises tissue tension by restricting the actomyosin contractility to the apical membranes of outflow tract cells. The tissue-scale polarisation of actomyosin contractility is required for cardiac looping that occurs concurrently with chamber ballooning. Taken together, our data reveal that instructive PCP signals couple cardiac chamber expansion with cardiac looping through the organ-scale polarisation of actomyosin-based tissue tension.},
  language  = {en}
}
@article{MerksSwinarskiMeyeretal.2018,
  author    = {Merks, Anne Margarete and Swinarski, Marie and Meyer, Alexander Matthias and M{\"u}ller, Nicola Victoria and {\"O}zcan, Ismail and Donat, Stefan and Burger, Alexa and Gilbert, Stephen and Mosimann, Christian and Abdelilah-Seyfried, Salim and Panakova, Daniela},
  title     = {Planar cell polarity signalling coordinates heart tube remodelling through tissue-scale polarisation of actomyosin activity},
  series = {Nature Communications},
  volume    = {9},
  journal   = {Nature Communications},
  publisher = {Nature Publ. Group},
  address   = {London},
  issn      = {2041-1723},
  doi       = {10.1038/s41467-018-04566-1},
  pages     = {15},
  year      = {2018},
  abstract  = {Development of a multiple-chambered heart from the linear heart tube is inherently linked to cardiac looping. Although many molecular factors regulating the process of cardiac chamber ballooning have been identified, the cellular mechanisms underlying the chamber formation remain unclear. Here, we demonstrate that cardiac chambers remodel by cell neighbour exchange of cardiomyocytes guided by the planar cell polarity (PCP) pathway triggered by two non-canonical Wnt ligands, Wnt5b and Wnt11. We find that PCP signalling coordinates the localisation of actomyosin activity, and thus the efficiency of cell neighbour exchange. On a tissue-scale, PCP signalling planar-polarises tissue tension by restricting the actomyosin contractility to the apical membranes of outflow tract cells. The tissue-scale polarisation of actomyosin contractility is required for cardiac looping that occurs concurrently with chamber ballooning. Taken together, our data reveal that instructive PCP signals couple cardiac chamber expansion with cardiac looping through the organ-scale polarisation of actomyosin-based tissue tension.},
  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}
}