xi, 38 p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / A critical question for developmental biology is the mechanism by which cells make fate decisions. In the hematopoietic system, stem cells differentiate into several different cell types, but the mechanisms that affect this process are incompletely known. Understanding these mechanisms is important because abnormal regulation of hematopoiesis can result in disease.
STAT1 protein plays crucial roles in mediating innate immunity by transducing interferon signals, but recent results have also related STAT1 to hematopoietic cell differentiation. Here we cloned a previously uncharacterized zebrafish co-ortholog of the human STAT1 gene we call stat1b and investigated the functions of two zebrafish Stat1 proteins in hematopoiesis. The advantage of the zebrafish model is that, due to a whole genome duplication (WGD), some human genes have two co-orthologs in zebrafish. During evolution, co-orthologs have retained or acquired similar, complimentary, or new functions.
Both stat1a and stat1b encode all four characteristic domains of the human STAT1 protein. Phylogenetic and conserved synteny analyses showed that stat1b and stat1a arose as duplicates in the teleost genome duplication event, and these analyses clarified the historical origin of the entire vertebrate STAT gene family. RT-PCR demonstrated maternal expression of both stat1a and stat1b . Expression of stat1b, but not stat1a, was detected in hematopoietic domains of embryos by in situ hybridization. Morpholino knockdown of stat1b , but not stat1a, mRNA expression resulted in a decrease in expression of the myeloid cell marker genes spi and mpx and an increase in expression of the hematopoietic progenitor marker gene scl and the erythrocyte marker gene gatal. These results show that in zebrafish, Stat1b protein functions in the commitment of hematopoietic cells to a myeloid cell fate. / Committee in charge: William Cresko, Chairperson, Biology;
John Postlethwait, Advisor, Biology;
Judith Eisen, Member, Biology;
Jan Spitsbergen, Member, Not from U of O;
J. Andrew Berglund, Outside Member, Chemistry
| Identifer | oai:union.ndltd.org:uoregon.edu/oai:scholarsbank.uoregon.edu:1794/10913 |
| Date | 06 1900 |
| Creators | Song, Hao |
| Publisher | University of Oregon |
| Source Sets | University of Oregon |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Relation | University of Oregon theses, Dept. of Biology, Ph. D., 2010; |
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