Suk-Won Jin, Ph.D.
Assistant Professor
Joint appointment with the Carolina Cardiovascular Biology Center

Education:

PhD, University of Michigan, 2000

Endothelial Cell Specification and Vascular Tube Morphogenesis

The main scientific interest of my laboratory is to understand how endothelial cells are specified and how these cells form vascular tubes. We use zebrafish, Danio rerio, as a model system to address these questions.

Current Projects

1. Understanding molecular and cellular mechanisms of angioblast specification

It has been hypothesized that endothelial cells and hematopoietic stem cells share common precursor population, the hemangioblasts. Evidences from the in vitro studies and cell culture experiments suggest the existence of these cells. However, it is still not clear whether hemangioblasts exist during normal development, and if so, how these two lineages separate. Using the combination of single cell labeling and lineage tracing, I have recently shown that the hemangioblasts exist during development (Fig.1). In addition, I've shown that Notch signaling appears to negatively regulate endothelial cell differentiation from hemangioblasts. Inhibition of Notch signaling increases the number of endothelial cells by three folds at the expense of hematopoietic stem cells, suggesting that Notch signaling pathway promote hematopoietic stem cell fate over endothelial cell fate in nascent hemangioblasts. I am planning to continue studying the differentiation of hemangioblasts in several known mutant background to investigate the role of various signaling pathways on the segregation of hemangioblast lineage.

2. Molecular and Genetic Analyses of Vascular Specific Mutations

From recently completed screen, several mutations affecting vascular development have been identified. Using flk1:EGFP transgenic lines (Fig.2) which expresses GFP in all endothelial cells, we categorized these mutations into four classes: mutations affecting angioblast specification (Fig.3), mutations affecting vascular tube formation, mutations affecting angiogenesis and remodeling process, and mutations affecting maintenance of vasculature. Among these, I am interested in first two classes of mutations. Currently, all mutations are mapped on the respective linkage groups. I will pursue positional cloning of the aforementioned mutants, and analyze their phenotype with molecular, genetic, and biochemical approaches to understand the functions of the loci affected by these mutations during vascular development.

	Fig.1 In vivo labeling of hemagioblast Click image for larger view.

Embryos transgenic for flk1:GFP and gata1:DsRed were injected with caged Fluorescein (FITC) at the 1-cell stage and then a single cell was activated by laser at 6hpf. (A) lateral view of the activated cell. (B) Brightfield picture of 30 hpf embryo, box indicates the area shown in C-J. (C-J) Lateral confocal sections of single labeled hemangioblast in a 30hpf embryo within the region defined by the box in (C, G) flk-1:GFP marking endothelial cells. (D,H) gata1::DsRed marking erythrocytes. (E, I) Uncaged FITC showing progeny of a single labeled cell. (F) Merge of C-E showing labeled endothelial cell. (J) Merge of G-I showing labeled erythrocyte.

Fig.2 Analyses of wildtype vasculature using flk1:GFP transgenic line Click image for larger view.

(A) Bright field micrograph of a 60 hpf old flk1:GFP transgenic embryo. Line indicates the position of the section shown in C. (B) Epifluorescence micrograph of the same embryo. (C) Transverse sections visualized for flk1::GFP (green), Fibronectin (blue), and ß-catenin (red). The flk1::GFP signal (green) and Fibronectin signal (blue) of the outlined areas are also shown separately in D and E.

Fig.3 Novel mutation groom of cloche (grc) affects angioblast specification Click image for larger view.

(A) Bright field micrograph of a 18 hpf old grc mutant embryo (left) with its wildtype sibling (right). (B) Epifluorescence micrograph of the same embryos. (C) Bright field micrograph of a 36 hpf old grc mutant embryo (bottom) with its wildtype sibling (top). (D) Epifluorescence micrograph of the same embryos. Notice drastic reduction of endothelial cells in mutant embryo compared to its wildtype sibling.

Publications

Vogeli KW*, Jin SW*, Martin G and Stainier DYR. (2006) A Common Progenitor for Hematopoietic and Endothelial Lineages in the Zebrafish Gastrula. Nature 443(7109):337-9. (*: Equally contributed)

Jin SW, Beis D, Chen JN, Mitchell TS and Stainier DYR. (2005) Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development 132(23):5199-209.

Beis D, Bartman T, Jin SW, Scott IC, D'Amico LA, Ober EA, Verkade H, Frantsve J, Field HA, Wehman A, Baier H, Tallafuss A, Bally-Cuif L, Chen JN, Stainier DY and Jungblut B. (2005) Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development. Development. 132(18):4193-4204

Bree RT, McLoughlin S, Jin SW, McMeel OM, Stainier DY, Grealy M and Byrnes L. (2005) nanor, a novel zygotic gene, is expressed initially at the midblastula transition in zebrafish. Biochem. Biophys. Res. Commun. 333(3):722-728

Qian F, Zhen F, Ong C, Jin SW, Meng Soo H, Stainier DY, Lin S, Peng J and Wen Z. (2005) Microarray analysis of zebrafish cloche mutant using amplified cDNA and identification of potential downstream target genes. Dev. Dyn. 233(3):1163-1172

Cho S, SW Jin, Cohen A and Ellis RE. (2004) A Caenorhabditid phylogeny shows frequent loss of introns during nematode evolution. Genome Research 14(7):1207-20.

Ober EA, Olofsson B, Makinen T, Jin SW, Shoji W, Koh GY, Alitalo K and Stainier DY. (2004) Vegfc is required for vascular development and endoderm morphogenesis in zebrafish. EMBO Rep. 5(1):78-84

Parker LH, Schmidt M, Jin SW, Gray AM, Beis D, Pham T, Frantz G, Palmieri S, Hillan K, Stainier DY, De Sauvage FJ, Ye W. (2004) The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation. Nature. 425(6984):754-758

Jin SW, Kimble J and Ellis RE. (2001) Regulation of Cell Fate in Caenorhabditis. elegans by a Novel Cytoplasmic Polyadenylation Element Binding Protein. Dev. Biol. 229, 537-553.

Stansberry J, Baude EJ, Taylor MK, Chen PJ, Jin SW, Ellis RE and Ulher MD. (2001) A cGMP-dependent protein kinase is implicated in wild-type motility in C. elegans. J. Neurochem. 76, 1177-87.

Chen PJ, Cho S, Jin SW, Ellis RE. (2001) Specification of germ cell fates by fog-3 has been conserved during nematode evolution. Genetics 158, 1513-25.

Jin SW, Arno N, Cohen A, Shah A, Chen N, Xu Q and Ellis RE. (2001) In Caenorhabditis elegans, the RNA-Binding Domains of the Cytoplasmic Polyadenylation Element Binding Protein FOG-1 Are Needed to Regulate Germ Cell Fates. Genetics 159, 1617-1630.