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 Blood, 15 July 2005, Vol. 106, No. 2, pp. 521-530.
Prepublished online as a Blood First Edition Paper on April 12, 2005; DOI 10.1182/blood-2004-11-4541.

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Submitted November 30, 2004
Accepted March 22, 2005

Mutant specific gene programs in the zebrafish

Gerhard J Weber, Sung E Choe, Kimberly A Dooley, Noelle N Paffett-Lugassy, Yi Zhou, and Leonard I Zon*

Children's Hospital Stem Cell Program, Department of Hematology/Oncology, Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA, USA
Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

* Corresponding author; email: zon{at}enders.tch.harvard.edu.

Hematopoiesis involves the production of stem cells, followed by the orchestrated differentiation of the blood lineages. Genetic screens in zebrafish have identified mutants with defects that disrupt specific stages of hematopoiesis and vasculogenesis, including cloche, spadetail (tbx16), moonshine (tif1g), bloodless, and vlad tepes (gata1) mutants. To better characterize the blood program, gene expression profiling was carried out in these mutants and in scl-morphants (sclmo). Distinct gene clusters were demarcated by stage specific and mutant specific gene regulation. These were found to correlate with the transcriptional program of hematopoietic progenitor cells, as well as of the erythroid, myeloid, and vascular lineages. Among these, several novel hematopoietic and vascular genes were detected, for instance the erythroid transcription factors znfl2 and ncoa4. A specific regulation was found for myeloid genes as they were more strongly expressed in vlt mutants, compared to other erythroid mutants. A unique gene expression pattern of upregulated isoprenoid synthesis genes was found in cloche and sclmo, possibly in migrating cells. In conjunction with the high conservation of vertebrate hematopoiesis, the comparison of transcriptional profiles in zebrafish blood mutants represents a versatile and powerful tool to elucidate the genetic regulation of blood and blood vessel development.


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