Zebrafish scl functions independently in hematopoietic and endothelial development

被引:111
作者
Dooley, KA
Davidson, AJ
Zon, LI
机构
[1] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA
[2] Dana Farber Canc Inst, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
关键词
scl; hematopoiesis; vasculogenesis; angiogenesis; zebrafish;
D O I
10.1016/j.ydbio.2004.09.004
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The SCL transcription factor is critically important for vertebrate hematopoiesis and angiogenesis, and has been postulated to induce hemangioblasts, bipotential precursors for blood and endothelial cells. To investigate the function of scl during zebrafish hematopoietic and endothelial development, we utilized site-directed, anti-sense morpholinos to inhibit scl mRNA. Knockdown of scl resulted in a loss of primitive and definitive hematopoietic cell lineages. However, the expression of early hematopoietic genes, gata2 and lmo2, was unaffected, suggesting that hematopoietic cells were present but unable to further differentiate. Using gene expression analysis and Visualization of vessel formation in live animals harboring an lmo2 promoter-green fluorescent protein reporter transgene (Tg(lmo2:EGFP)), we show that angioblasts were specified normally in the absence of scl, but later defects in angiogenesis were evident. While scl was not required for angioblast specification, forced expression of exogenous scl caused ail expansion of both hematopoietic and endothelial gene expression, and a loss of somitic tissue. In cloche and spadetail mutants, forced expression of scl resulted in an expansion of hematopoietic but not endothelial tissue. Surprisingly, in cloche, lmo2 was not induced in response to scl over-expression. Taken together, these findings support distinct roles for scl in hematopoietic and endothelial development, downstream of hemangioblast development. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:522 / 536
页数:15
相关论文
共 73 条
[1]  
ALADHAMI MA, 1977, DEV GROWTH DIFFER, V19, P171, DOI 10.1111/j.1440-169X.1977.00171.x
[2]   Regulation of the stem cell leukemia (SCL) gene:: A tale of two fishes [J].
Barton, LM ;
Göttgens, B ;
Gering, M ;
Gilbert, JGR ;
Grafham, D ;
Rogers, J ;
Bentley, D ;
Patient, R ;
Green, AR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (12) :6747-6752
[3]   THE GENE SCL IS EXPRESSED DURING EARLY HEMATOPOIESIS AND ENCODES A DIFFERENTIATION-RELATED DNA-BINDING MOTIF [J].
BEGLEY, CG ;
APLAN, PD ;
DENNING, SM ;
HAYNES, BF ;
WALDMANN, TA ;
KIRSCH, IR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (24) :10128-10132
[4]   Myelopoiesis in the zebrafish, Danio rerio [J].
Bennett, CM ;
Kanki, JP ;
Rhodes, J ;
Liu, TX ;
Paw, BH ;
Kieran, MW ;
Langenau, DM ;
Delahaye-Brown, A ;
Zon, LI ;
Fleming, MD ;
Look, AT .
BLOOD, 2001, 98 (03) :643-651
[5]   Insights into early vasculogenesis revealed by expression of the ETS-domain transcription factor Fli-1 in wild-type and mutant zebrafish embryos [J].
Brown, LA ;
Rodaway, ARF ;
Schilling, TF ;
Jowett, T ;
Ingham, PW ;
Patient, RK ;
Sharrocks, AD .
MECHANISMS OF DEVELOPMENT, 2000, 90 (02) :237-252
[6]   Characterization of embryonic globin genes of the zebrafish [J].
Brownlie, A ;
Hersey, C ;
Oates, AC ;
Paw, BH ;
Falick, AM ;
Witkowska, HE ;
Flint, J ;
Higgs, D ;
Jessen, J ;
Bahary, N ;
Zhu, H ;
Lin, S ;
Zon, L .
DEVELOPMENTAL BIOLOGY, 2003, 255 (01) :48-61
[7]   Isolation and characterization of runxa and runxb, zebrafish members of the runt family of transcriptional regulators [J].
Burns, CE ;
DeBlasio, T ;
Zhou, Y ;
Zhang, J ;
Zon, L ;
Nimer, SD .
EXPERIMENTAL HEMATOLOGY, 2002, 30 (12) :1381-1389
[8]   THE TAL-GENE UNDERGOES CHROMOSOME-TRANSLOCATION IN T-CELL LEUKEMIA AND POTENTIALLY ENCODES A HELIX LOOP HELIX PROTEIN [J].
CHEN, Q ;
CHENG, JT ;
TSAI, LH ;
SCHNEIDER, N ;
BUCHANAN, G ;
CARROLL, A ;
CRIST, W ;
OZANNE, B ;
SICILIANO, MJ ;
BAER, R .
EMBO JOURNAL, 1990, 9 (02) :415-424
[9]  
Choi K, 1998, DEVELOPMENT, V125, P725
[10]   Chromatin immunoselection defines a TAL-1 target gene [J].
Cohen-Kaminsky, S ;
Maouche-Chrétien, L ;
Vitelli, L ;
Vinit, MA ;
Blanchard, I ;
Yamamoto, M ;
Peschle, C ;
Roméo, PH .
EMBO JOURNAL, 1998, 17 (17) :5151-5160