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The vertebrate vasculature displays a highly reproducible and pervasive anatomy, required for the delivery and exchange of gases, hormones, metabolites and immunity factors. Consequently, defective vessel growth contributes to the pathogenesis of multiple human diseases.
To understand the genetic pathways and cellular strategies used by developing vessels to acquire their architecture, we are using genetic approaches and imaging tools to study vascular development in zebrafish. In particular, we are focusing on answering the following questions:
We hope that the answers to these questions will allow us to contribute to the development of therapies aimed at the regulation of blood vessel growth, like anti-cancer treatments and ischemic tissue re-vascularization.
The transparent and externally developing zebrafish embryo is the only genetic system in which blood vessel development can be visualized in vivo and in real time. In addition, animals with defective vessels survive for long periods of time due to passive oxygen diffusion, providing the opportunity to study both early and late embryonic stages of vascular patterning. In our studies, we employ transgenic animals carrying vascular fluorescent reporters and high-resolution imaging methods, such as confocal microscopy and microangiography to study gene-specific loss of function phenotypes generated by mutagenesis or morpholino injection.
Want to watch an example of this powerful combination? See the development of the zebrafish trunk vasculature (formation of the intersomitic vessels) in a normal embryo and in an animal lacking plxnD1 activity.
Confocal time-lapse movies of the development of the intersomitic vessels in TG(fli1-EGFP)y1 embryos (Lateral views, from 20 to 32 hours post fertilization. Dorsal is to the top and anterior is to the left). Note that in wild type embryos the intersomitic vessels sprout at regular intervals and display thin and dynamic filopodia-like projections, which are absent from the Dorsal Aorta. The path followed by the intersomitic vessels prefigures their final shape. By contrast, in animals lacking the function of the endothelial-specific receptor plxnD1 the intersomitic sprouts grow at irregular intervals and form an aberrant interconnected vascular network due to the formation of ectopic interconnections.
Learn more at the Torres-Vazquez Laboratory Homepage.
Aminoacyl-Transfer RNA Synthetase Deficiency Promotes Angiogenesis via the Unfolded Protein Response Pathway
Castranova, Daniel; Davis, Andrew E; Lo, Brigid D; Miller, Mayumi F; Paukstelis, Paul J; Swift, Matthew R; Pham, Van N; Torres-Vazquez, Jesus; Bell, Kameha; Shaw, Kenna M; Kamei, Makoto; Weinstein, Brant M. Aminoacyl-Transfer RNA Synthetase Deficiency Promotes Angiogenesis via the Unfolded Protein Response Pathway. Arteriosclerosis, thrombosis, & vascular biology. 2016 Jan 28;36(4):655-662 (2044032)
Development of functional hindbrain oculomotor circuitry independent of both vascularization and neuronal activity in larval zebrafish
Ulrich, F; Grove, C; Torres-Vazquez, J; Baker, R. Development of functional hindbrain oculomotor circuitry independent of both vascularization and neuronal activity in larval zebrafish. Current neurobiology. 2016 2016;7(2):62-73 (2227072)
Reck enables cerebrovascular development by promoting canonical Wnt signaling
Ulrich, Florian; Carretero-Ortega, Jorge; Menendez, Javier; Narvaez, Carlos; Sun, Belinda; Lancaster, Eva; Pershad, Valerie; Trzaska, Sean; Veliz, Evelyn; Kamei, Makoto; Prendergast, Andrew; Kidd, Kameha R; Shaw, Kenna M; Castranova, Daniel A; Pham, Van N; Lo, Brigid D; Martin, Benjamin L; Raible, David W; Weinstein, Brant M; Torres-Vazquez, Jesus. Reck enables cerebrovascular development by promoting canonical Wnt signaling. Development. 2016 Mar 15;143(6):1055-1055 (2047282)
Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue
Minchin, James E N; Dahlman, Ingrid; Harvey, Christopher J; Mejhert, Niklas; Singh, Manvendra K; Epstein, Jonathan A; Arner, Peter; Torres-Vazquez, Jesus; Rawls, John F. Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue. Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2015 Mar 23;112(14):4363-4368 (1519492)
Origin, Specification, and Plasticity of the Great Vessels of the Heart
Nagelberg, Danielle; Wang, Jinhu; Su, Rina; Torres-Vazquez, Jesus; Targoff, Kimara L; Poss, Kenneth D; Knaut, Holger. Origin, Specification, and Plasticity of the Great Vessels of the Heart. Current biology. CB. 2015 Aug 6;25(16):2099-2110 (1721552)