Brant Weinstein's Section on Vertebrate Organogenesis studies blood and lymphatic vessel formation during vertebrate embryogenesis. Blood vessels supply every tissue and organ with oxygen, nutrients, and cellular and humoral factors. Lymphatic vessels drain fluids and macromolecules from the interstitial spaces of tissues, returning them to the blood circulation, and play an important role in immune responses. Understanding the formation of blood and lymphatic vessels is of intense clinical interest because of the roles that both types of vessels play in cancer and ischemia. The zebrafish, a small tropical freshwater fish, possesses a unique combination of features that make it particularly suitable for studying vessel formation; the fish is a genetically tractable vertebrate with a physically accessible, optically clear embryo. These features are highly advantageous for studying vascular development, permitting observation of every vessel in the living animal and simple, rapid screening for even subtle vascular-specific defects.
The Weinstein lab has pioneered use of the zebrafish as an important new model system for studying vascular biology. The group developed many of the now widely used tools for studying the zebrafish vasculature, including a confocal microangiography method, a detailed anatomical atlas of the vasculature, numerous vascular-specific transgenic lines, and methods for high-resolution in vivo time-lapse imaging of developing blood vessels. Using these and other methods, the group has made a number of novel and important discoveries, including a pathway for artery specification, a role for neuronal guidance factors in vascular patterning, a mechanism for vascular tube formation in vivo; and identification of the lymphatic vascular system in zebrafish. Current studies use genetic screening, experimental analysis, sophisticated imaging technologies, and other methods to examine developmental angiogenesis and lymphangiogenesis, including cues directing vascular patterning and morphogenesis, regulation of vascular integrity, and assembly of the lymphatic system.
Butler MG, Iben JR, Marsden KC, Epstein JA, Granato M, Weinstein BM. SNPfisher: tools for probing genetic variation in laboratory-reared zebrafish. Development. 2015 Apr 15;142(8):1542-52. doi: 10.1242/dev.118786. Epub 2015 Mar 26. PMID: 25813542
Pan W, Pham VN, Stratman AN, Castranova D, Kamei M, Kidd KR, Lo BD, Shaw KM, Torres-Vazquez J, Mikelis CM, Gutkind JS, Davis GE, Weinstein BM. CDP-diacylglycerol synthetase-controlled phosphoinositide availability limits VEGFA signaling and vascular morphogenesis. Blood. 2012 Jul 12;120(2):489-98. doi: 10.1182/blood-2012-02-408328. Epub 2012 May 30. PMID: 22649102
Avraham-Davidi I, Ely Y, Pham VN, Castranova D, Grunspan M, Malkinson G, Gibbs-Bar L, Mayseless O, Allmog G, Lo B, Warren CM, Chen TT, Ungos J, Kidd K, Shaw K, Rogachev I, Wan W, Murphy PM, Farber SA, Carmel L, Shelness GS, Iruela-Arispe ML, Weinstein BM, Yaniv K. ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1. Nat Med. 2012 Jun;18(6):967-73. doi: 10.1038/nm.2759. PMID: 22581286
- Cha, Y.-R., Fujita, M., Butler, M., Isogai, S., Kochhan, E., Siekmann, A. F., and Weinstein, B. M. 2012. Chemokine signaling directs trunk lymphatic network formation along the preexisting blood vasculature. Developmental Cell 22:824-836
- Fujita, M., Cha, Y. R., Roman, B. L., Weinstein, B. M. 2011. Assembly and patterning of the vascular network of the vertebrate hindbrain. Development 138:1705-1715.
- Gore, A. V., Swift, M., Cha, Y. R., Lo, B. D., McKinney, M. C., Li, W., Castranova, D., Davis, A., Mukouyama, Y., and Weinstein, B. M. 2011. Vegfc/Vegfr3-Dependent Angiogenesis is Regulated by Canonical Rspo1/Wnt Signaling. Development 138:4875-4886.
- Gore, A. V., Lampugnani, M. G., Dye, L., Dejana, E., and Weinstein, B. M. 2009. Combinatorial interaction between CCM pathway genes precipitates hemorrhagic stroke. Disease Models and Mechanisms 1, 275-281.
- Kamei M, Saunders WB, Bayless KJ, Dye L, Davis GE, Weinstein BM. Endothelial tubes assemble from intracellular vacuoles in vivo. Nature. 2006 Jul 27;442(7101):453-6. PMID: 16799567
- Yaniv K, Isogai S, Castranova D, Dye L, Hitomi J, Weinstein BM. Live imaging of lymphatic development in the zebrafish. Nat Med. 2006 Jun;12(6):711-6. PMID: 16732279
- Torres-Vázquez J, Gitler AD, Fraser SD, Berk JD, Van N Pham, Fishman MC, Childs S, Epstein JA, Weinstein BM. Semaphorin-plexin signaling guides patterning of the developing vasculature. Dev Cell. 2004 Jul;7(1):117-23. PMID: 15239959