The Drosophila genes disconnected and disco-related are redundant with respect to larval head development and accumulation of mRNAs from deformed target genes.

HOM-C/hox genes specify body pattern by encoding regionally expressed transcription factors that activate the appropriate target genes necessary for differentiation of each body region. The current model of target gene activation suggests that interactions with cofactors influence DNA-binding ability and target gene activation by the HOM-C/hox proteins. Currently, little is known about the specifics of this process because few target genes and fewer cofactors have been identified. We undertook a deficiency screen in Drosophila melanogaster in an attempt to identify loci potentially encoding cofactors for the protein encoded by the HOM-C gene Deformed (Dfd). We identified a region of the X chromosome that, when absent, leads to loss of specific larval mouthpart structures producing a phenotype similar to that observed in Dfd mutants. The phenotype is correlated with reduced accumulation of mRNAs from Dfd target genes, though there appears to be no effect on Dfd protein accumulation. We show that these defects are due to the loss of two functionally redundant, neighboring genes encoding zinc finger transcription factors, disconnected and a gene we call disco-related. We discuss the role of these genes during differentiation of the gnathal segments and, in light of other recent findings, propose that regionally expressed zinc finger proteins may play a central role with the HOM-C proteins in establishing body pattern.

Oncogenic retroviruses of cattle, chickens and turkeys: potential infectivity and oncogenicity for humans.

Reticuloendotheliosis virus naturally infects and cause lymphoid leukosis in chickens and turkeys. We investigated whether it can infect/transfect a variety of human cells in vitro. Successful infection and transfection were achieved with limited replication of virus. These findings, together with the knowledge that other oncogenic retroviruses of chickens and cattle, viz. The avian leukosis/sarcoma viruses and bovine leukemia virus show similar infectivity/oncogencity in vitro for humans, and the recent demonstration of antibodies to avian leukosis/sarcoma virus and reticuloendotheliosis virus in human sera, suggest that these viruses may have a role in the etiology of certain cancers in humans. There is now urgent need to investigate this, particularly because recent epidemiological studies consistently demonstrate excess of cancers in groups occupationally exposed to these viruses.

Molecular characterization and rescue of acatalasemic mutants of Drosophila melanogaster.

The enzyme catalase protects aerobic organisms from oxygen-free radical damage by converting hydrogen peroxide to molecular oxygen and water before it can decompose to form the highly reactive hydroxyl radical. Hydroxyl radicals are the most deleterious of the activated oxygen intermediates found in aerobic organisms. If formed, they can react with biological molecules in their proximity; the ensuing damage has been implicated in the increasing risk of disease and death associated with aging. To study further the regulation and role of catalase we have undertaken a molecular characterization of the Drosophila catalase gene and two potentially acatalasemic alleles. We have demonstrated that a previously existing allele, Catn4, likely contains a null mutation, a mutation which blocks normal translation of the encoded mRNA. The Catn1 mutation appears to cause a significant change in the protein sequence; however, it is unclear why this change leads to a nonfunctioning protein. Viability of these acatalasemic flies can be restored by transformation with the wild-type catalase gene; hence, we conclude that the lethality of these genotypes is due solely to the lack of catalase. The availability of flies with transformed catalase genes has allowed us to address the effect of catalase levels on aging in Drosophila. Though lack of catalase activity caused decreased viability and life span, increasing catalase activity above wild-type levels had no effect on normal life span.

Identification and characterization of a gene activated by the deformed homeoprotein.

In Drosophila, the homeotic genes encode transcription factors which control segment identity during embryogenesis by specifying the appropriate set of 'target' genes necessary to produce the individual segmental characteristics. Though we know much about the homeotic genes and the proteins they encode, we know little of their targets. Here we identify and characterize one such target gene, a gene activated by the product of the homeotic gene Deformed. DNA binding assays and expression of reporter gene constructs indicate that activation of this gene requires a direct interaction between the Deformed protein and an upstream enhancer element at this target gene. However, although Deformed is required to activate this gene in cells of the maxillary segment, ectopically expressed Deformed does not activate the gene in other regions of the embryo. We conclude from this and other observations that additional factors may be required to activate the target gene, and, therefore, Deformed may participate in either a combinatorial or hierarchical activation signal in the maxillary cells. This newly identified gene encodes a novel protein of unknown function, though proteins with similar amino acid composition have been found. The pattern of transcript accumulation during embryogenesis indicates that this gene may be regulated by other homeoproteins in addition to Deformed.