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- Alvarez, Alberto, et al.
(författare)
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VEGF Receptor Tyrosine Kinases : Key Regulators of Vascular Function
- 2017
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Ingår i: Protein Kinases In Development And Disease. - : Elsevier. - 9780128015131 ; 123, s. 433-
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Bokkapitel (refereegranskat)abstract
- Vascular endothelial growth factor receptor (VEGFR) tyrosine kinases are key regulators of vascular development in vertebrates. Their activation is regulated through a family of secreted glycoproteins, the vascular endothelial growth factors (VEGFs). Expression, proteolytic processing, and diffusion range of VEGF proteins need to be tightly regulated, due to their crucial roles in development. While some VEGFs form concentration gradients across developing tissues and act as morphogenes, others function as inhibitors of receptor activation and downstream signaling. Ligand-induced receptor dimerization leads to activation of the intrinsic tyrosine kinase activity, which results in autophosphorylation of the receptors and in turn triggers the recruitment of interacting proteins as well as the initiation of downstream signaling. Although many biochemical details of VEGFR signaling have been revealed, the in vivo relevance of certain signaling aspects still remains to be demonstrated. Here, we highlight basic principles of VEGFR signaling and discuss its crucial role during development of the vascular system in mammals.
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| 4. |
- Jung, Bongnam, et al.
(författare)
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Visualization of vascular mural cells in developing brain using genetically labeled transgenic reporter mice
- 2018
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE PUBLICATIONS INC. - 0271-678X .- 1559-7016. ; 38:3, s. 456-468
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Tidskriftsartikel (refereegranskat)abstract
- The establishment of a fully functional blood vascular system requires elaborate angiogenic and vascular maturation events in order to fulfill organ-specific anatomical and physiological needs. Although vascular mural cells, i.e. pericytes and vascular smooth muscle cells, are known to play fundamental roles during these processes, their characteristics during vascular development remain incompletely understood. In this report, we utilized transgenic reporter mice in which mural cells are genetically labeled to examine developing vascular mural cells in the central nervous system (CNS). We found platelet-derived growth factor receptor beta gene (Pdgfrb)-driven EGFP reporter expression as a suitable marker for vascular mural cells at the earliest stages of mouse brain vascularization. Furthermore, the combination of Pdgfrb and NG2 gene (Cspg4) driven reporter expression increased the specificity of brain vascular mural cell labeling at later stages. The expression of other known pericyte markers revealed time-,region-and marker-specific patterns, suggesting heterogeneity in mural cell maturation. We conclude that transgenic reporter mice provide an important tool to explore the development of CNS pericytes in health and disease.
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