Disease relevance of srp

• Given the similarities of Srp and Lz to mammalian GATA and AML1 proteins, observations in Drosophila are likely to have broad implications for understanding mammalian hematopoiesis and leukemias [1].

High impact information on srp

• Genetic interactions between dominant pnr mutants bearing lesions situated in the amino-terminal zinc finger of the GATA domain and ush mutants have been described [2].
• end-1 encodes an apparent GATA factor that specifies the endoderm precursor in Caenorhabditis elegans embryos [3].
• We focus on the regulation of two mesodermal genes: bagpipe (bap), which defines the anlagen of the visceral musculature of the midgut, and serpent (srp), which marks the anlagen of the fat body [4].
• Over the past year, vertebrate GATA factors have been found to participate directly in several signal-transduction pathways [5].
• Here we show that srp encodes different isoforms, generated by alternative splicing, that contain either only a C-finger (SrpC) or both a C- and an N-finger (SrpNC) [6].

Biological context of srp

• 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 [7].
• Here we show that Srp, Lozenge, and U-shaped interact in different combinations to regulate crystal cell lineage commitment [7].
• The GATA factor, Serpent, directly regulated the activity of both enhancers [8].
• We demonstrate that this cell loss is a consequence of programmed cell death (apoptosis) in ush, hnt and srp, but not in tup [9].
• We present evidence that srp expression in different precursor fat cells is controlled by independent cis-acting regulatory regions, and we have tested the role of trans-acting factors in the specification of some of these cells [10].

Anatomical context of srp

• Both isoforms individually rescue blood cell formation that is lacking in an srp null mutation [6].
• 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 [7].
• In Drosophila, the GATA factor gene serpent (srp) is critical for differentiation of the endoderm [11].
• Our data suggest that Serpent is involved in the distinction between a systemic response in the yolk/fat body and a local immune response in epithelial cells [12].
• The GATA, Friend of GATA, and Runt homology domain protein families function during hematopoiesis to promote progenitor cell development and regulate lineage commitment and differentiation [13].

Physical interactions of srp

• A Drosophila GATA family member that binds to Adh regulatory sequences is expressed in the developing fat body [14].

Regulatory relationships of srp

• Conversely, overexpression of dGATAe induced ectopic expression of endodermal markers even in the absence of srp activity [11].

Other interactions of srp

• Our knowledge of endoderm development is limited; however, recent studies suggest that cooperation between the HNF3/Fork head and GATA transcription factors is crucial for endoderm specification [15].
• These observations indicate that GATAe activates a major subset of genes in the midgut, and some other pathway(s) downstream of srp activates other genes [16].
• We propose that Serpent plays a key role in tissue-specific expression of immunity genes, by priming them for inducible activation by Rel proteins in response to infection [17].
• A nuclear DNA-binding activity interacts with the Cecropin A1 GATA motif with the same properties as the Drosophila GATA factor Serpent [17].
• A UAS site substitution approach to the in vivo dissection of promoters: interplay between the GATAb activator and the AEF-1 repressor at a Drosophila ecdysone response unit [18].

Analytical, diagnostic and therapeutic context of srp

• Site-directed mutagenesis of this element shows that these Tinman sites are critical to dSUR expression, and further genetic manipulations suggest that the GATA transcription factor Pannier is synergistically involved in cardiac-restricted dSUR expression in vivo [19].
• One of these sequences, TGATAA, bound in vitro to Drosophila melanogaster box A binding factor protein, as shown by gel mobility shift assays [20].

References