Disease relevance of lz

• 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 lz

• Binding of the cell-specific Lozenge protein is also required for activation, and overlapping Lozenge protein distribution and DER signaling establishes expression in a subset of equivalent cells competent to respond to Sevenless [2].
• The transcription factor Lz (Lozenge), which resembles human AML1 (acute myeloid leukemia- 1) protein, is necessary for the development of crystal cells during embryonic and larval hematopoiesis [1].
• Lozenge directly activates argos and klumpfuss to regulate programmed cell death [3].
• Loss of either aos or klu reduces cell death, suggesting that Lz promotes apoptosis at least in part by regulating aos and klu [3].
• Serrate signaling through the Notch pathway is critical in the regulation of Lz expression and the specification of crystal cell precursors, thus providing a key distinction between the two lineages [4].

Biological context of lz

• Combinatorial interactions of serpent, lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis [5].
• We show that reducing the activity of the Drosophila Runx protein Lozenge (Lz) during pupal development causes a decrease in cell death in the eye [3].
• These results provide novel insights into the control of programmed cell death (PCD) by Lz during Drosophila eye development [3].
• We show here that Lz plays a crucial role in governing the fate of two groups of cells that are born in a single round of mitosis in the larval eye disc [6].
• In contrast, in a second group of cells, the Lz protein confers proper photoreceptor identity by positively regulating the homeo box gene Bar. Additionally, our genetic analysis suggests that Lz interacts with the Ras pathway to determine photoreceptor cell fate [6].

Anatomical context of lz

• Lozenge, a Runx protein homologue, and Glial cells missing-1 and -2 are essential for crystal cell and plasmatocyte production, respectively [5].
• The lozenge (lz) gene encodes a transcription factor involved in prepatterning photoreceptor precursors in the developing Drosophila eye [6].
• LZ function is also required in hematopoiesis for the specification of a Drosophila blood cell lineage [7].

Associations of lz with chemical compounds

• We provide evidence that Sine oculis and Glass are the two major activators of Lz expression during eye development [8].

Co-localisations of lz

• Expression studies show that Big brother is a nuclear protein that co-localizes with both Lozenge and Runt in the eye imaginal disc [9].

Regulatory relationships of lz

• Notably, we demonstrate that GCM/GCM2 play a key role in controlling the size of the crystal cell population by inhibiting lz activation and maintenance [10].
• We present evidence that amos is required for olfactory sensilla and is regulated by the prepattern gene lozenge [11].
• Yan regulates Lozenge during Drosophila eye development [12].

Other interactions of lz

• We show that, surprisingly, gcm is initially expressed in all prohemocytes but is rapidly downregulated in the anterior-most row of prohemocytes, which then initiates lz expression [10].
• amos, a proneural gene for Drosophila olfactory sense organs that is regulated by lozenge [11].
• The nuclear localization and stability of Big brother protein is mediated through the formation of heterodimeric complexes between Big brother and either Lozenge or Runt [9].
• We propose that upregulated Lozenge acts as a cofactor to alter Pointed affinity, by a mechanism that is recapitulated in mammalian development [12].
• A second gene, D-Pax2, genetically interacts with lozenge [13].

Analytical, diagnostic and therapeutic context of lz

• We use site-directed mutagenesis and yeast two-hybrid analysis to show that conserved amino acids within the alternate Lozenge exon are important for interaction with Pointed [14].

References