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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04159nam a2200409 4500 | |
| 001 | oai:DiVA.org:uu-347778 | |
| 003 | SwePub | |
| 008 | 180407s2018 | |||||||||||000 ||eng| | |
| 020 | a 9789151303178q print | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3477782 URI |
| 040 | a (SwePub)uu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a vet2 swepub-contenttype |
| 072 | 7 | a dok2 swepub-publicationtype |
| 100 | 1 | a Castro, Marcou Uppsala universitet,Institutionen för immunologi, genetik och patologi4 aut0 (Swepub:uu)marca302 |
| 245 | 1 0 | a Cellular and molecular roles for CDC42 in angiogenesis |
| 264 | 1 | a Uppsala :b Acta Universitatis Upsaliensis,c 2018 |
| 300 | a 52 s. | |
| 338 | a electronic2 rdacarrier | |
| 490 | 0 | a Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,x 1651-6206 ;v 1458 |
| 520 | a Angiogenesis is the physiological process by which new blood vessels grow and critically depends on the interplay between the major vascular units: endothelial cells, pericytes and smooth muscle cells. Dysfunction and mispatterning of blood vessels are associated with the progression of many vascular complications, and therefore, understanding the causes of vascular dysmorphia is a central question in vascular biology. CDC42 is a small GTPase known to regulate a diverse array of cellular functions in endothelial cells, however, its contribution to vascular development in vivo remains incompletely understood. The overall aim of this thesis work is to investigate the role of CDC42 during angiogenesis in the central nervous system, using an inducible endothelial-specific Cdc42 knockout model.In Paper I, I investigate which CDC42-dependent functions operational in vivo are of relevance for angiogenic sprouting, and how they contribute to blood vessel morphogenesis. Analysis of distinct cellular behaviours shows that CDC42 is critically required for proper EC dispersion in the vasculature and that it regulates sprouting angiogenesis and endothelial axial polarity.In Paper II, I explore the in vivo consequences of Cdc42 deletion for vascular morphogenesis, leading to the appearance of capillary-venous malformations in the brain, resembling the human disease of cerebral cavernous malformations. I aimed to understand how this type of vascular malformations arise and was been able to identify the MEKK3-ERK5-KLF2/4 molecular signalling pathway and other cellular events as the trigger factors that may be responsible for these malformations.Paper III redirects focus to the physiological roles of another protein, GPR116, in modulating blood-brain barrier permeability and pathologic angiogenesis in the central nervous system.In summary, these findings reveal crucial roles of endothelial CDC42 during angiogenesis and further uncover its potential relevance in the molecular pathogenesis of cerebrovascular malformations. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng |
| 653 | a CDC42 | |
| 653 | a angiogenesis | |
| 653 | a endothelial cell | |
| 653 | a vascular malformation | |
| 653 | a Biology with specialization in Molecular Cell Biology | |
| 653 | a Biologi med inriktning mot molekylär cellbiologi | |
| 700 | 1 | a Betsholtz, Christer,c Professoru Uppsala universitet,Institutionen för immunologi, genetik och patologi4 ths |
| 700 | 1 | a Laviña, Bàrbara,c Researcheru Uppsala universitet,Institutionen för immunologi, genetik och patologi4 ths |
| 700 | 1 | a Benedito, Rui,c Professoru CNIC - Spanish Center for Cardiovascular Research4 opn |
| 710 | 2 | a Uppsala universitetb Institutionen för immunologi, genetik och patologi4 org |
| 856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1195927/FULLTEXT01.pdfx primaryx Raw objecty fulltext |
| 856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1195927/PREVIEW01.jpgx Previewy preview image |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-347778 |
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