The main interest in the lab is vertebrate organogenesis, in particular the development of both the lymphatic and blood vasculature as well as the formation of mineralized bone tissue. Our approach to better understand this process with relevance to both embryogenesis and medicine is phenotype driven: we isolate zebrafish mutants that exhibit defects in endothelial or osteoblast behavior or function, and then study the affected gene on the molecular, cellular, and the organ level. We use mainly the zebrafish due to its amenability for genetic screens and its small size which permits studying a particular organ in its entity. In addition the transparency of zebrafish larvae is a key feature which allows in vivo imaging of the behavior of osteoblasts and endothelial cells on a single cell level over time.
About the research
Huitema, L.F.A., Apschner, A., Logister, I., Spoorendonk, K.M., Bussmann, J., Hammond, C.L., and Schulte-Merker, S. (2012) Entpd5 is essential for skeletal mineralization and regulates phosphate homeostasis in zebrafish. PNAS 109(52), 21372-7.
Bos, F.L., Caunt, M., Peterson-Maduro, J., Planas-Paz, L., Kowalski, J., Karpanen, T., van Impel, A., Tong, R., Ernst, J.A., Korving, J., van Es., J.H., Lammert, E., Duckers, H.J., and Schulte-Merker, S. (2011) CCBE1 Is Essential for Mammalian Lymphatic Vascular Development and Enhances the Lymphangiogneic Effect of Vascular Endothelial Growth Factor-C In Vivo. Circulation Research109(5): 486-91.
Hogan, B.M., Bos, F., Bussmann, J., Witte, M., Chi, N., Duckers, H., Schulte-Merker, S. (2009) Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nature Genet. 41: 396-398.
Alders, M., Hogan, B.M., Gjini, E., Salehi, F., Al-Gazali, L., Hennekam, E.A., Holmberg, E.E., Mannens, M.M.A.M., Mulder, M.F., Offerhaus, G.J.A., Prescott, T.E., Schroor, E.J., Verheij, J.B.G.M., Witte, M., Zwijnenburg, P.J., Vikkula, M., Schulte-Merker, S. & Hennekam, R.C. (2009) Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. Nature Genetics, published online: Nature Genetics 41: 1272-1274.
Spoorendonk, K., Peterson-Maduro, J., Renn, J., Trowe, T., Kranenbarg, S., Winkler, C., Schulte-Merker, S. (2008) Retinoic Acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton. Development 135: 3765-3774.
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