Our goal is to understand the underlying molecular and genetic mechanisms involved in the initiation of hematopoietic differentiation and proliferation during embryogenesis. Towards this goal, we have chosen two of the earliest defined markers of vertebrate hematopoietic development, GATA- l and GATA-2, as entry points into the hematopoietic program of the zebrafish. To identify factors that function to initiate GATA-1 and GATA-2 expression or interact with them to regulate hematopoiesis, we will seek to establish a comprehensive profile of genes specifically co-expressed with GATA-1 and GATA-2; to study the function of these genes through genetic and transgenic analysis; and to elucidate the transcriptional mechanisms controlling hematopoietic expression of GATA-2. We believe that studies from zebrafish should ultimately help us understand how hematopoietic development is controlled in human being.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK054508-08
Application #
6773146
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Badman, David G
Project Start
1998-03-06
Project End
2008-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
8
Fiscal Year
2004
Total Cost
$296,160
Indirect Cost
Name
University of California Los Angeles
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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
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
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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