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Helen White-Cooper

Publications and source records attributed to Helen White-Cooper.

9 recordsLinked to original sources
PubMed2025

A single-nucleus transcriptomic atlas of the adult Aedes aegypti mosquito.

The female Aedes aegypti mosquito's remarkable ability to hunt humans and transmit pathogens relies on her unique biology. Here, we present the Aedes aegypti Mosquito Cell Atlas, a comprehensive single-nucleus RNA sequencing dataset of more than 367,000 nuclei from 19 dissected tissues of adult female and male Aedes aegypti, providing cellular-level resolution of mosquito biology. We identify novel cell types and expand our understanding of sensory neuron organization of chemoreceptors to all sensory tissues. Our analysis uncovers male-specific cells and sexually dimorphic gene expression in the antenna and brain. In female mosquitoes, we find that glial cells in the brain, rather than neurons, undergo the most extensive transcriptional changes following blood feeding. Our findings provide insights into the cellular basis of mosquito behavior and sexual dimorphism. The Aedes aegypti Mosquito Cell Atlas resource enables systematic investigation of cell type-specific expression across all mosquito tissues.

Aedes aegypti↗
PubMed2004

Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes.

The retinoblastoma tumor suppressor protein (pRb) regulates gene transcription by binding E2F transcription factors. pRb can recruit several repressor complexes to E2F bound promoters; however, native pRb repressor complexes have not been isolated. We have purified E2F/RBF repressor complexes from Drosophila embryo extracts and characterized their roles in E2F regulation. These complexes contain RBF, E2F, and Myb-interacting proteins that have previously been shown to control developmentally regulated patterns of DNA replication in follicle cells. The complexes localize to transcriptionally silent sites on polytene chromosomes and mediate stable repression of a specific set of E2F targets that have sex- and differentiation-specific expression patterns. Strikingly, seven of eight complex subunits are structurally and functionally related to C. elegans synMuv class B genes, which cooperate to control vulval differentiation in the worm. These results reveal an extensive evolutionary conservation of specific pRb repressor complexes that physically combine subunits with established roles in the regulation of transcription, DNA replication, and chromatin structure.

Amino Acid Sequence↗
PubMed2004

Gene structure and molecular analysis of Arabidopsis thaliana ALWAYS EARLY homologs.

Drosophila always early (aly) is essential for spermatogenesis, and is related to the LIN-9 protein of Caenorhabditis elegans; lin-9 is a class B Synthetic Multivulva gene (synMuvB) required for gonadal sheath development. Aly/LIN-9 have two conserved regions, called domains 1 and 2, which have been identified in homologous proteins from several multicellular eukaryotes, including the model plant Arabidopsis thaliana. We cloned and sequenced cDNAs of three different A. thaliana ALWAYS EARLY homologs (AtALY1, AtALY2 and AtALY3), analysed the expression pattern of these three genes and show that AtALY1, like Aly, is nuclear localised. We also demonstrate that the plant homologs of aly/lin-9 contain an additional N-terminal myb domain not present in the animal Aly/LIN-9 proteins, and that part of the ALY/LIN-9 conserved domain 1 in the predicted plant proteins is related to the TUDOR domain.

Amino Acid Sequence↗
PubMed2004

The essential role of PP1beta in Drosophila is to regulate nonmuscle myosin.

Reversible phosphorylation of myosin regulatory light chain (MRLC) is a key regulatory mechanism controlling myosin activity and thus regulating the actin/myosin cytoskeleton. We show that Drosophila PP1beta, a specific isoform of serine/threonine protein phosphatase 1 (PP1), regulates nonmuscle myosin and that this is the essential role of PP1beta. Loss of PP1beta leads to increased levels of phosphorylated nonmuscle MRLC (Sqh) and actin disorganisation; these phenotypes can be suppressed by reducing the amount of active myosin. Drosophila has two nonmuscle myosin targeting subunits, one of which (MYPT-75D) resembles MYPT3, binds specifically to PP1beta, and activates PP1beta's Sqh phosphatase activity. Expression of a mutant form of MYPT-75D that is unable to bind PP1 results in elevation of Sqh phosphorylation in vivo and leads to phenotypes that can also be suppressed by reducing the amount of active myosin. The similarity between fly and human PP1beta and MYPT genes suggests this role may be conserved.

Amino Acid Sequence↗
PubMed2004

Spatial and temporal control of mitotic cyclins by the Gnu regulator of embryonic mitosis in Drosophila.

Mutation of the Drosophila maternal cell cycle regulator, Gnu, results in loss of embryonic mitosis and the onset of excessive nuclear DNA replication. The Gnu phosphoprotein is normally synthesized in nurse cells and transported to the developing oocyte. We created a gnuGFP-bcd3'UTR transgene using the gnu promoter and bicoid 3'UTR, that translates GnuGFP only on egg activation from a localized anterior source. This transgene was able to rescue the sterility of gnu mutant females. Gnu is therefore first required after egg activation for polar body condensation and zygotic mitoses. Embryos containing pronounced anterior-posterior gradients of Gnu activity demonstrate that Gnu regulates mitotic activity by promoting cyclin B stability. Our gnuGFP-bcd3'UTR vector provides a novel experimental strategy to analyse the temporal requirement and role of cell cycle regulators including potential sperm-supplied factors in eggs and embryos.

Animals↗
PubMed2004

Regulation of transcription of meiotic cell cycle and terminal differentiation genes by the testis-specific Zn-finger protein matotopetli.

A robust developmentally regulated and cell type specific transcriptional programme is activated in primary spermatocytes in preparation for differentiation of the male gametes during spermatogenesis. Work in Drosophila is beginning to reveal the genetic networks that regulate this gene expression. The Drosophila aly-class meiotic arrest loci are essential for activation of transcription of many differentiation-specific genes, as well as several genes important for meiotic cell cycle progression, thus linking meiotic cell cycle progression to cellular differentiation during spermatogenesis. The three previously described aly-class proteins (aly, comr and achi/vis) form a complex and are associated with chromatin in primary spermatocytes. We identify, clone and characterize a new aly-class meiotic arrest gene, matotopetli (topi), which encodes a testis-specific Zn-finger protein that physically interacts with Comr. The topi mutant phenotype is most like achi/vis in that topi function is not required for the nuclear localization of Aly or Comr, but is required for their accumulation on chromatin. Most target genes in the transcriptional programme depend on both topi and achi/vis; however, a small subset of target genes are differentially sensitive to loss of topi or achi/vis, suggesting that these aly-class predicted DNA binding proteins can act independently in some contexts.

Amino Acid Sequence↗
PubMed2003

Transcriptional activation in Drosophila spermatogenesis involves the mutually dependent function of aly and a novel meiotic arrest gene cookie monster.

In Drosophila spermatogenesis, meiotic cell cycle progression and cellular differentiation are linked by the function of the meiotic arrest genes. The meiotic arrest genes control differentiation by regulating the transcriptional activation of many differentiation-specific genes. The meiotic arrest genes have been subdivided into aly and can classes, based on the mechanism by which they control cell cycle progression. aly has previously been shown to encode a chromatin-associated protein. We present the identification, cloning and characterisation of a novel Drosophila meiotic arrest gene, cookie monster (comr), that has a mutant phenotype indistinguishable from that of aly. A null mutant allele of comr is viable but male sterile. Mutant primary spermatocytes fail to initiate transcription of a large number of genes, and arrest before entry into the meiotic divisions. In adult males, expression of comr is testis specific, low levels of transcripts are detected at other stages of development. comr encodes a novel acidic protein, which is nuclear and primarily localised to regions of chromatin in primary spermatocytes. The nuclear localisation of Aly and Comr proteins are mutually dependent. Finally, we show that active RNA polymerase II is found in distinct domains in the nucleus that constitute a subset of the total Comr stained chromatin.

Alleles↗
PubMed2003

Drosophila TGIF is essential for developmentally regulated transcription in spermatogenesis.

We have investigated the role of TGIF, a TALE-class homeodomain transcription factor, in Drosophila development. In vertebrates, TGIF has been implicated, by in vitro analysis, in several pathways, most notably as a repressor modulating the response to TGFbeta signalling. Human TGIF has been associated with the developmental disorder holoprosencephaly. Drosophila TGIF is represented by the products of two tandemly repeated highly similar genes, achintya and vismay. We have generated mutations that delete both genes. Homozygous mutant flies are viable and appear morphologically normal, but the males are completely sterile. The defect lies at the primary spermatocyte stage and differentiation is blocked prior to the onset of the meiotic divisions. We show that mutants lacking TGIF function fail to activate transcription of many genes required for sperm manufacture and of some genes required for entry into the meiotic divisions. This groups TGIF together with two other genes producing similar phenotypes, always early and cookie monster, as components of the machinery required for the activation of the spermatogenic programme of transcription. TGIF is the first sequence-specific transcription factor identified in this pathway. By immunolabelling in mouse testes we show that TGIF is expressed in the early stages of spermatogenesis consistent with a conserved role in the activation of the spermatogenesis transcription programme.

Amino Acid Sequence↗