RESUMO
Successful development of a multicellular organism depends on the finely tuned orchestration of cell proliferation, differentiation and apoptosis from embryogenesis through adulthood. The MYB-gene family encodes sequence-specific DNA-binding transcription factors that have been implicated in the regulation of both normal and neoplastic growth. The Drosophila Myb protein, DMyb (and vertebrate B-Myb protein), has been shown to be part of the dREAM/MMB complex, a large multi-subunit complex, which in addition to four Myb-interacting proteins including Mip130, contains repressive E2F and pRB proteins. This complex has been implicated in the regulation of DNA replication within the context of chorion gene amplification and transcriptional regulation of a wide array of genes. Detailed phenotypic analysis of mutations in the Drosophila myb gene, Dm myb, has revealed a previously undiscovered function for the dREAM/MMB complex in regulating programmed cell death (PCD). In cooperation with the pro-apoptotic protein Grim and dREAM/MMB, DMyb promotes the PCD of specified sensory organ precursor daughter cells in at least two different settings in the peripheral nervous system: the pIIIb precursor of the neuron and sheath cells in the posterior wing margin and the glial cell in the thoracic microchaete lineage. Unlike previously analyzed settings, in which the main role of DMyb has been to antagonize the activities of other dREAM/MMB complex members, it appears to be the critical effector in promoting PCD. The finding that Dm myb and grim are both involved in regulating PCD in two distinct settings suggests that these two genes may often work together to mediate PCD.
Assuntos
Caspases/genética , Proteínas de Ciclo Celular/genética , Morte Celular , Proteínas de Drosophila/genética , Drosophila/genética , Neurônios/metabolismo , Neuropeptídeos/genética , Proteínas Proto-Oncogênicas c-myb/genética , Asas de Animais/metabolismo , Animais , Apoptose , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Caspases/metabolismo , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular , Linhagem da Célula , Proliferação de Células , Replicação do DNA , Drosophila/embriologia , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Fatores de Transcrição E2F/genética , Fatores de Transcrição E2F/metabolismo , Genes myb , Neuropeptídeos/metabolismo , Proteínas Proto-Oncogênicas c-myb/metabolismo , Fatores de Transcrição , Asas de Animais/embriologiaRESUMO
PDP1 is a basic leucine zipper (bZip) transcription factor that is expressed at high levels in the muscle, epidermis, gut and fat body of the developing Drosophila embryo. We have identified three mutant alleles of Pdp1, each having a similar phenotype. Here, we describe in detail the Pdp1 mutant allele, Pdp1(p205), which is null for both Pdp1 RNA and protein. Interestingly, homozygous Pdp1(p205) embryos develop normally, hatch and become viable larvae. Analyses of Pdp1 null mutant embryos reveal that the overall muscle pattern is normal as is the patterning of the gut and fat body. Pdp1(p205) larvae also appear to have normal muscle and gut function and respond to ecdysone. These larvae, however, are severely growth delayed and arrested. Furthermore, although Pdp1 null larvae live a normal life span, they do not form pupae and thus do not give rise to eclosed flies. The stunted growth of Pdp1(p205) larvae is accompanied by defects in mitosis and endoreplication similar to that associated with nutritional deprivation. The cellular defects resulting from the Pdp1(p205) mutation are not cell autonomous. Moreover, PDP1 expression is sensitive to nutritional conditions, suggesting a link between nutrition, PDP1 isotype expression and growth. These results indicate that Pdp1 has a critical role in coordinating growth and DNA replication.
