Mentors

Shuo Lin, Ph.D.
Luisa Iruela-Arispe, Ph.D.

Research Interests:

Imaging Blood Vessel Formation in Transgenic Zebrafish

Blood vessel formation is tightly linked to different types of cancer in humans. The zebrafish has recently emerged as an advantageous model organism to study how the evolutionary conserved network of vertebrate blood vessels arises during development. Recently, I demonstrated a critical role for a novel ETS1-related protein Etsrp, encoding an ETS domain transcription factor, in regulating zebrafish vascular development (Sumanas and Lin, 2006). In the etsrp-morpholino (MO) injected embryos, in which Etsrp translation is downregulated, blood vessel progenitors, angioblasts, do not migrate, differentiate, or express any vascular markers. In the figure, vasculature-specific flk1-GFP expression in the etsrp-MO injected embryos is nearly completely absent from axial and intersegmental vessels (lower panel), compared with control uninjected embryos (upper panel).

Etsrp is the earliest known gene specifically restricted to the vascular precursor cells, thus marking angioblasts during their earliest stages of formation. To identify and study early angioblasts in live embryos, I am currently generating etsrp-GFP transgenic line in which green fluorescent protein (GFP) will be expressed under the control of etsrp promoter / enhancer. Formation and migration of angioblasts and their coalescence into blood vessels will be observed and studied using time-lapse imaging of live transgenic zebrafish embryos. Etsrp is expressed earlier than other known vascular markers, such as, thus revealing previously unknown regions of vasculogenesis. In addition to the endothelial cells of known blood vessels, etsrp is expressed in a previously unknown group of cells in the pronephric region which appear to migrate posteriorly and do not express other vascular markers. These cells may represent the precursors of kidney and gut vessels and have not been described previously. Imaging of etsrp-GFP expression in live embryos will determine the identity and migratory properties of these cells. Fate of etsrp-expressing cells will be determined by UV-uncaging of fluorescent dyes in selected cells and following their development in live embryos. These studies will greatly expand our knowledge of the mechanisms of vasculogenesis and angiogenesis.

Assistant Professor
Division of Developmental Biology
Cincinnati Children’s Hospital Foundation
Cincinnati, Ohio

Sumanas S, Lin S. (2006). Ets1-related protein is a key regulator of vasculogenesis in zebrafish. PLOS Biol 4, e10.

Kim HJ, Sumanas S, Palencia-Desai S, Dong Y, Chen J-N, Lin S. (2006). Genetic analysis of early endocrine pancreas formation in zebrafish. Mol Endocrinol 20, 194-203.

Sumanas S, Jorniak T, Lin S. (2005). Identification of novel vascular endothelial-specific genes by the microarray analysis of the zebrafish cloche mutants. Blood 106, 534-541.

Sumanas S, Zhang B, Dai R, Lin S. (2005). 15-zinc finger protein Bloody Fingers is required for zebrafish morphogenetic movements during neurulation. Dev Biol 283, 85-96.

Kim HJ, Schleiffarth JR, Jessurun J, Sumanas S, Petryk A, Lin S, Ekker SC. (2005). Wnt5 Signaling in Vertebrate Pancreas Development. BMC Biol 3, 23.

Sumanas S, Lin S. (2004). Zebrafish as a model system for drug target screening and validation (Review). Drug Disc Today: Targets 3, 89-96.

Sumanas S, Larson J, Bever MM. (2003). Zebrafish chaperone protein GP96 is involved in otolith formation during ear development. Dev Biol 261, 443-455.

Sumanas S, Larson J. (2002). Morpholino phosphorodiamidate oligonucleotides in zebrafish: a recipe for functional genomics? (Review). Brief Funct Genomic Proteomic 1, 239-256.

Sumanas S, Kim HJ, Hermanson S, and Ekker SC. (2002). Lateral line, nervous system, and maternal expression of Frizzled7a during zebrafish embryogenesis. Mech Dev 115, 107-111.

Sumanas S, Kim HJ, Hermanson S and Ekker SC. (2001). Zebrafish frizzled-2 morphant displays defects in body axis elongation. Genesis 30, 114-118.

Sumanas S, and Ekker SC. (2001). Xenopus frizzled-7 morphant displays defects in dorso-ventral patterning and convergent extension movements during gastrulation. Genesis 30, 119-122.

Sumanas S, and Ekker SC. (2001). Xenopus frizzled-5: a frizzled family member expressed exclusively in the neural retina of the developing eye. Mech Dev 103, 133-136.

Sumanas S, Strege P, Heasman J, and Ekker SC. (2000). The putative Wnt receptor Xenopus frizzled-7 functions upstream of beta-catenin in vertebrate dorso-ventral mesoderm patterning. Development 127, 1981-1990.

Nasevicius A, Hyatt T, Kim H, Guttman J, Walsh E, Sumanas S, Wang Y and Ekker SC. (1998). Evidence for a frizzled-mediated wnt pathway required for zebrafish dorsal mesoderm formation. Development 125, 4283-4292.