Our goal is to understand the underlying mechanisms involved in regulating lineage specification of hematopoietic stem cells (HSC) and vascular angioblast cells from mesoderm during embryogenesis. Towards this goal we have chosen etsrp, one of the earliest lineage specific genes involved in hematopoietic and vascular development, as an entry point to dissect this process in zebrafish. Specifically, we will analyze functions of etsrp in definitive hematopoiesis, elucidate mechanisms regulating its specific expression, identify and characterize its biological targets. Since genes we propose to study are highly conserved between fish and mammals information obtained from zebrafish should be useful for understanding human pathogenesis and designing better therapeutics for hematological and vascular diseases.

Public Health Relevance

Zebrafish is a popular model organism for studying development, physiology and human diseases. We use state of the art technologies to identify and characterize essential new genes required for the formation of blood stem cells and vascular progenitors in zebrafish. Since these genes are highly conserved between fish and human our studies will provide valuable information for understanding human hematopoietic and vascular diseases and assisting design of novel therapeutic approaches.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZRG1-HEME-G (02))
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Bishop, Terry Rogers
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University of California Los Angeles
Schools of Arts and Sciences
Los Angeles
United States
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Lin, Sijie; Zhao, Yan; Nel, Andre E et al. (2013) Zebrafish: an in vivo model for nano EHS studies. Small 9:1608-18
Veldman, Matthew B; Zhao, Chengjian; Gomez, Gustavo A et al. (2013) Transdifferentiation of fast skeletal muscle into functional endothelium in vivo by transcription factor Etv2. PLoS Biol 11:e1001590
Zhao, Yan; Lin, Shuo (2013) Essential role of SH3-domain GRB2-like 3 for vascular lumen maintenance in zebrafish. Arterioscler Thromb Vasc Biol 33:1280-6
Gomez, Gustavo; Lee, Jae-Hyung; Veldman, Matthew B et al. (2012) Identification of vascular and hematopoietic genes downstream of etsrp by deep sequencing in zebrafish. PLoS One 7:e31658
Huang, Haigen; Lindgren, Anne; Wu, Xinrong et al. (2012) High-throughput screening for bioactive molecules using primary cell culture of transgenic zebrafish embryos. Cell Rep 2:695-704
Zhang, Ying; Morimoto, Kenji; Danilova, Nadia et al. (2012) Zebrafish models for dyskeratosis congenita reveal critical roles of p53 activation contributing to hematopoietic defects through RNA processing. PLoS One 7:e30188
Veldman, Matthew B; Lin, Shuo (2012) Etsrp/Etv2 is directly regulated by Foxc1a/b in the zebrafish angioblast. Circ Res 110:220-9
Danilova, Nadia; Sakamoto, Kathleen M; Lin, Shuo (2011) Ribosomal protein L11 mutation in zebrafish leads to haematopoietic and metabolic defects. Br J Haematol 152:217-28
Zhong, Hanbing; Wang, Danyang; Wang, Nan et al. (2011) Combinatory action of VEGFR2 and MAP kinase pathways maintains endothelial-cell integrity. Cell Res 21:1080-7
Ren, Xi; Gomez, Gustavo A; Zhang, Bo et al. (2010) Scl isoforms act downstream of etsrp to specify angioblasts and definitive hematopoietic stem cells. Blood 115:5338-46

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