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  • 1
    Online Resource
    Online Resource
    Protecting and Diversifying the Germline
    Oxford University Press (OUP) ; 2018
    In:  Genetics Vol. 208, No. 2 ( 2018-02-01), p. 435-471
    Details
    In: Genetics, Oxford University Press (OUP), Vol. 208, No. 2 ( 2018-02-01), p. 435-471
    Abstract: Gametogenesis represents the most dramatic cellular differentiation pathways in both female and male flies. At the genome level, meiosis ensures that diploid germ cells become haploid gametes. At the epigenome level, extensive changes are required to turn on and shut off gene expression in a precise spatiotemporally controlled manner. Research applying conventional molecular genetics and cell biology, in combination with rapidly advancing genomic tools have helped us to investigate (1) how germ cells maintain lineage specificity throughout their adult reproductive lifetime; (2) what molecular mechanisms ensure proper oogenesis and spermatogenesis, as well as protect genome integrity of the germline; (3) how signaling pathways contribute to germline-soma communication; and (4) if such communication is important. In this chapter, we highlight recent discoveries that have improved our understanding of these questions. On the other hand, restarting a new life cycle upon fertilization is a unique challenge faced by gametes, raising questions that involve intergenerational and transgenerational epigenetic inheritance. Therefore, we also discuss new developments that link changes during gametogenesis to early embryonic development—a rapidly growing field that promises to bring more understanding to some fundamental questions regarding metazoan development.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    URL: Article
    DOI: 10.1534/genetics.117.300208
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 2
    Online Resource
    Online Resource
    Regulation of genes affecting body size and innate immunity by the DBL-1/BMP-like pathway in Caenorhabditis elegans
    Springer Science and Business Media LLC ; 2010
    In:  BMC Developmental Biology Vol. 10, No. 1 ( 2010-12)
    Details
    In: BMC Developmental Biology, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2010-12)
    Abstract: Bone morphogenetic proteins (BMPs) are members of the conserved transforming growth factor β (TGFβ superfamily, and play many developmental and homeostatic roles. In C. elegans , a BMP-like pathway, the DBL-1 pathway, controls body size and is involved in innate immunity. How these functions are carried out, though, and what most of the downstream targets of this pathway are, remain unknown. Results We performed a microarray analysis and compared expression profiles of animals lacking the SMA-6 DBL-1 receptor, which decreases pathway signaling, with animals that overexpress DBL-1 ligand, which increases pathway signaling. Consistent with a role for DBL-1 in control of body size, we find positive regulation by DBL-1 of genes involved in physical structure, protein synthesis and degradation, and metabolism. However, cell cycle genes were mostly absent from our results. We also identified genes in a hedgehog -related pathway, which may comprise a secondary signaling pathway downstream of DBL-1 that controls body size. In addition, DBL-1 signaling up-regulates pro-innate immunity genes. We identified a reporter for DBL-1 signaling, which is normally repressed but is up-regulated when DBL-1 signaling is reduced. Conclusions Our results indicate that body size in C. elegans is controlled in part by regulation of metabolic processes as well as protein synthesis and degradation. This supports the growing body of evidence that suggests cell size is linked to metabolism. Furthermore, this study discovered a possible role for hedgehog -related pathways in transmitting the BMP-like signal from the hypodermis, where the core DBL-1 pathway components are required, to other tissues in the animal. We also identified the up-regulation of genes involved in innate immunity, clarifying the role of DBL-1 in innate immunity. One of the highly regulated genes is expressed at very low levels in wild-type animals, but is strongly up-regulated in Sma/Mab mutants, making it a useful reporter for DBL-1/BMP-like signaling in C. elegans .
    Type of Medium: Online Resource
    ISSN: 1471-213X
    URL: Article
    DOI: 10.1186/1471-213X-10-61
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
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  • 3
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    Online Resource
    Symmetry from Asymmetry or Asymmetry from Symmetry?
    Cold Spring Harbor Laboratory ; 2017
    In:  Cold Spring Harbor Symposia on Quantitative Biology Vol. 82 ( 2017), p. 305-318
    Details
    In: Cold Spring Harbor Symposia on Quantitative Biology, Cold Spring Harbor Laboratory, Vol. 82 ( 2017), p. 305-318
    Type of Medium: Online Resource
    ISSN: 0091-7451 , 1943-4456
    URL: Article
    DOI: 10.1101/sqb.2017.82.034272
    RVK:
    WB 5133
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2017
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    detail.hit.zdb_id: 2467510-6
    SSG: 12
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  • 4
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    Online Resource
    BMP signaling requires retromer-dependent recycling of the type I receptor
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 7 ( 2014-02-18), p. 2578-2583
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 7 ( 2014-02-18), p. 2578-2583
    Abstract: The transforming growth factor β (TGFβ) superfamily of signaling pathways, including the bone morphogenetic protein (BMP) subfamily of ligands and receptors, controls a myriad of developmental processes across metazoan biology. Transport of the receptors from the plasma membrane to endosomes has been proposed to promote TGFβ signal transduction and shape BMP-signaling gradients throughout development. However, how postendocytic trafficking of BMP receptors contributes to the regulation of signal transduction has remained enigmatic. Here we report that the intracellular domain of Caenorhabditis elegans BMP type I receptor SMA-6 (small-6) binds to the retromer complex, and in retromer mutants, SMA-6 is degraded because of its missorting to lysosomes. Surprisingly, we find that the type II BMP receptor, DAF-4 (dauer formation-defective-4), is retromer-independent and recycles via a distinct pathway mediated by ARF-6 (ADP-ribosylation factor-6). Importantly, we find that loss of retromer blocks BMP signaling in multiple tissues. Taken together, our results indicate a mechanism that separates the type I and type II receptors during receptor recycling, potentially terminating signaling while preserving both receptors for further rounds of activation.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1319947111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
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    SSG: 11
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Direct measurements of meltwater runoff on the Greenland ice sheet surface
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 50 ( 2017-12-12)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 50 ( 2017-12-12)
    Abstract: Meltwater runoff from the Greenland ice sheet surface influences surface mass balance (SMB), ice dynamics, and global sea level rise, but is estimated with climate models and thus difficult to validate. We present a way to measure ice surface runoff directly, from hourly in situ supraglacial river discharge measurements and simultaneous high-resolution satellite/drone remote sensing of upstream fluvial catchment area. A first 72-h trial for a 63.1-km 2 moulin-terminating internally drained catchment (IDC) on Greenland’s midelevation (1,207–1,381 m above sea level) ablation zone is compared with melt and runoff simulations from HIRHAM5, MAR3.6, RACMO2.3, MERRA-2, and SEB climate/SMB models. Current models cannot reproduce peak discharges or timing of runoff entering moulins but are improved using synthetic unit hydrograph (SUH) theory. Retroactive SUH applications to two older field studies reproduce their findings, signifying that remotely sensed IDC area, shape, and supraglacial river length are useful for predicting delays in peak runoff delivery to moulins. Applying SUH to HIRHAM5, MAR3.6, and RACMO2.3 gridded melt products for 799 surrounding IDCs suggests their terminal moulins receive lower peak discharges, less diurnal variability, and asynchronous runoff timing relative to climate/SMB model output alone. Conversely, large IDCs produce high moulin discharges, even at high elevations where melt rates are low. During this particular field experiment, models overestimated runoff by +21 to +58%, linked to overestimated surface ablation and possible meltwater retention in bare, porous, low-density ice. Direct measurements of ice surface runoff will improve climate/SMB models, and incorporating remotely sensed IDCs will aid coupling of SMB with ice dynamics and subglacial systems.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1707743114
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Natural genetic variation in Drosophila melanogaster reveals genes associated with Coxiella burnetii infection
    Oxford University Press (OUP) ; 2021
    In:  Genetics Vol. 217, No. 3 ( 2021-03-31)
    Details
    In: Genetics, Oxford University Press (OUP), Vol. 217, No. 3 ( 2021-03-31)
    Abstract: The gram-negative bacterium Coxiella burnetii is the causative agent of Query (Q) fever in humans and coxiellosis in livestock. Host genetics are associated with C. burnetii pathogenesis both in humans and animals; however, it remains unknown if specific genes are associated with severity of infection. We employed the Drosophila Genetics Reference Panel to perform a genome-wide association study to identify host genetic variants that affect host survival to C. burnetii infection. The genome-wide association study identified 64 unique variants (P  & lt; 10−5) associated with 25 candidate genes. We examined the role each candidate gene contributes to host survival during C. burnetii infection using flies carrying a null mutation or RNAi knockdown of each candidate. We validated 15 of the 25 candidate genes using at least one method. This is the first report establishing involvement of many of these genes or their homologs with C. burnetii susceptibility in any system. Among the validated genes, FER and tara play roles in the JAK/STAT, JNK, and decapentaplegic/TGF-β signaling pathways which are components of known innate immune responses to C. burnetii infection. CG42673 and DIP-ε play roles in bacterial infection and synaptic signaling but have no previous association with C. burnetii pathogenesis. Furthermore, since the mammalian ortholog of CG13404 (PLGRKT) is an important regulator of macrophage function, CG13404 could play a role in host susceptibility to C. burnetii through hemocyte regulation. These insights provide a foundation for further investigation regarding the genetics of C. burnetii susceptibility across a wide variety of hosts.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    URL: Article
    DOI: 10.1093/genetics/iyab005
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1477228-0
    SSG: 12
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