Biomedical subjects

Nancy Fossett

Publications and source records attributed to Nancy Fossett.

3 recordsLinked to original sources

PubMed2006

Regulation of Drosophila friend of GATA gene, u-shaped, during hematopoiesis: a direct role for serpent and lozenge.

Friend of GATA proteins interact with GATA factors to regulate development in a variety of tissues. We analyzed cis- and trans-regulation of the Drosophila gene, u-shaped, to better understand the transcriptional control of this important gene family during hematopoiesis. Using overlapping genomic fragments driving tissue-specific reporter-gene (lacZ) expression, we identified two minimal hematopoietic enhancers within the 7.4 kb region upstream of the transcription start site. One enhancer was active in all classes of hemocytes, whereas the other was active in hemocyte precursors and plasmatocytes only. The GATA factor, Serpent, directly regulated the activity of both enhancers. However, activity in the crystal cell lineage not only required Serpent but also the RUNX homologue, Lozenge. This is the first demonstration of GATA and RUNX direct regulation of Friend of GATA gene expression and provides additional evidence for the combinatorial control of crystal cell lineage commitment by Serpent, Lozenge, and U-shaped. In addition, we analyzed cis-regulation of ush expression in the lymph gland and identified similarities and differences between regulatory strategies used during embryonic and lymph gland hematopoiesis. The results of these studies provide information to analyze further the regulation of this conserved gene family and its role during hematopoietic lineage commitment.

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PubMed2005

Hemocyte development during Drosophila embryogenesis.

The model genetic organism Drosophila melanogaster has a rudimentary hematopoietic system with two embryonic blood cell types, crystal cells, and plasmatocytes. These distinct lineages provide the animal with an innate immune response and a means to remove apoptotic cells. Genetic analyses of Drosophila hematopoiesis have identified specific genes that function in blood cell formation. Complimentary deoxyribonucleic acid and antibody probes for these hematopoietic factors serve as important reagents to follow hemocyte lineage commitment and differentiation during embryogenesis. This is possible through methods described in this chapter on messenger ribonucleic acid localization by in situ hybridization and protein localization by immunohistochemical staining within hemocyte precursors and mature blood cells.

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PubMed2003

Combinatorial interactions of serpent, lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis.

The GATA factor Serpent (Srp) is required for hemocyte precursor formation during Drosophila hematopoiesis. These blood cell progenitors give rise to two distinct lineages within the developing embryo. Lozenge, a Runx protein homologue, and Glial cells missing-1 and -2 are essential for crystal cell and plasmatocyte production, respectively. In contrast U-shaped, a Friend of GATA class factor, antagonizes crystal cell formation. Here we show that Srp, Lozenge, and U-shaped interact in different combinations to regulate crystal cell lineage commitment. Coexpression of Srp and Lozenge synergistically activated the crystal cell program in both embryonic and larval stages. Furthermore, expression of Lozenge and SrpNC, a Srp isoform with N- and C-terminal zinc fingers, inhibited u-shaped expression, indicating that crystal cell activation coincided with the down-regulation of this repressor-encoding gene. In contrast, whereas U-shaped and SrpNC together blocked crystal cell production, coexpression of U-shaped with noninteracting Srp proteins failed to prevent overproduction of this hemocyte population. Such results indicated that U-shaped and SrpNC must interact to block crystal cell production. Taken together, these studies show that the specialized SrpNC isoform plays a pivotal role during crystal cell lineage commitment, acting as an activator or repressor depending on the availability of specific transcriptional coregulators. These findings provide definitive proof of the combinatorial regulation of hematopoiesis in Drosophila and an in vivo demonstration of GATA and Runx functional interaction in a blood cell commitment program.

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