Dana T Byrd

San Francisco State University, San Francisco, California, United States

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Publications (8)40.58 Total impact

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    ABSTRACT: The mesenchymal distal tip cell (DTC) provides the niche for Caenorhabditis elegans germline stem cells (GSCs). The DTC has a complex cellular architecture: its cell body caps the distal gonadal end and contacts germ cells extensively, but it also includes multiple cellular processes that extend along the germline tube and intercalate between germ cells. Here we use the lag-2 DTC promoter to drive expression of myristoylated GFP, which highlights DTC membranes and permits a more detailed view of DTC architecture. We find that short processes intercalating between germ cells contact more germ cells than seen previously. We define this region of extensive niche contact with germ cells as the DTC plexus. The extent of the DTC plexus corresponds well with the previously determined extent of the GSC pool. Moreover, expression of a differentiation marker increases as germ cells move out of the plexus. Maintenance of this DTC plexus depends on the presence of undifferentiated germ cells, suggesting that germ cell state can influence niche architecture. The roles of this DTC architecture remain an open question. One idea is that the DTC plexus delivers Notch signaling to the cluster of germ cells comprising the GSC pool; another idea is that the plexus anchors GSCs at the distal end.
    Full-text · Article · Feb 2014 · PLoS ONE
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    ABSTRACT: In Caenorhabditis elegans gonad morphogenesis, the final U-shapes of the two hermaphrodite gonad arms are determined by migration of the distal tip cells (DTCs). These somatic cells migrate in opposite directions on the ventral basement membrane until specific extracellular cues induce turning from ventral to dorsal and then centripetally toward the midbody region on the dorsal basement membrane. To dissect the mechanism of DTC turning, we examined the role of a novel gene, F40F11.2/mig-38, whose depletion by RNAi results in failure of DTC turning so that DTCs continue their migration away from the midbody region. mig-38 is expressed in the gonad primordium, and expression continues throughout DTC migration where it acts cell-autonomously to control DTC turning. RNAi depletion of both mig-38 and ina-1, which encodes an integrin adhesion receptor, enhanced the loss of turning phenotype indicating a genetic interaction between these genes. Furthermore, the integrin-associated protein MIG-15/Nck-interacting kinase (NIK) works with MIG-38 to direct DTC turning as shown by mig-38 RNAi with the mig-15(rh80) hypomorph. These results indicate that MIG-38 enhances the role of MIG-15 in integrin-dependent DTC turning. Knockdown of talin, a protein that is important for integrin activation, causes the DTCs to stop migration prematurely. When both talin and MIG-38 were depleted by RNAi treatment, the premature stop phenotype was suppressed. This suppression effect was reversed upon additional depletion of MIG-15 or its binding partner NCK-1. These results suggest that both talin and the MIG-15/NCK-1 complex promote DTC motility and that MIG-38 may act as a negative regulator of the complex. We propose a model to explain the dual role of MIG-38 in motility and turning.
    Preview · Article · Jun 2012 · Developmental Biology
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    Jamie M. Verheyden · Dana T. Byrd · Judith Kimble

    Preview · Article · Aug 2011 · Developmental Biology
  • Dana T. Byrd · Judith Kimble
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    ABSTRACT: The Caenorhabditis elegans gonad provides a well-defined model for a stem cell niche and its control of self-renewal and differentiation. The distal tip cell (DTC) forms a mesenchymal niche that controls germline stem cells (GSCs), both to generate the germline tissue during development and to maintain it during adulthood. The DTC uses GLP-1/Notch signaling to regulate GSCs; germ cells respond to Notch signaling with a network of RNA regulators to control the decision between self-renewal and entry into the meiotic cell cycle.
    No preview · Article · Dec 2009 · Seminars in Cell and Developmental Biology
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    ABSTRACT: The Caenorhabditis elegans germ line provides a model for understanding how signaling from a stem cell niche promotes continued mitotic divisions at the expense of differentiation. Here we report cellular analyses designed to identify germline stem cells within the germline mitotic region of adult hermaphrodites. Our results support several conclusions. First, all germ cells within the mitotic region are actively cycling, as visualized by bromodeoxyuridine (BrdU) labeling. No quiescent cells were found. Second, germ cells in the mitotic region lose BrdU label uniformly, either by movement of labeled cells into the meiotic region or by dilution, probably due to replication. No label-retaining cells were found in the mitotic region. Third, the distal tip cell niche extends processes that nearly encircle adjacent germ cells, a phenomenon that is likely to anchor the distal-most germ cells within the niche. Fourth, germline mitoses are not oriented reproducibly, even within the immediate confines of the niche. We propose that germ cells in the distal-most rows of the mitotic region serve as stem cells and more proximal germ cells embark on the path to differentiation. We also propose that C. elegans adult germline stem cells are maintained by proximity to the niche rather than by programmed asymmetric divisions.
    Preview · Article · Aug 2006 · Molecular Biology of the Cell
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    ABSTRACT: Kinesin-1 is a heterotetramer composed of kinesin heavy chain (KHC) and kinesin light chain (KLC). The Caenorhabditis elegans genome has a single KHC, encoded by the unc-116 gene, and two KLCs, encoded by the klc-1 and klc-2 genes. We show here that UNC-116/KHC and KLC-2 form a complex orthologous to conventional kinesin-1. KLC-2 also binds UNC-16, the C. elegans JIP3/JSAP1 JNK-signaling scaffold protein, and the UNC-14 RUN domain protein. The localization of UNC-16 and UNC-14 depends on kinesin-1 (UNC-116 and KLC-2). Furthermore, mutations in unc-16, klc-2, unc-116, and unc-14 all alter the localization of cargos containing synaptic vesicle markers. Double mutant analysis is consistent with these four genes functioning in the same pathway. Our data support a model whereby UNC-16 and UNC-14 function together as kinesin-1 cargos and regulators for the transport or localization of synaptic vesicle components.
    Full-text · Article · Mar 2005 · Molecular Biology of the Cell
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    ABSTRACT: Transport of synaptic components is a regulated process. Loss-of-function mutations in the C. elegans unc-16 gene result in the mislocalization of synaptic vesicle and glutamate receptor markers. unc-16 encodes a homolog of mouse JSAP1/JIP3 and Drosophila Sunday Driver. Like JSAP1/JIP3, UNC-16 physically interacts with JNK and JNK kinases. Deletion mutations in Caenorhabditis elegans JNK and JNK kinases result in similar mislocalization of synaptic vesicle markers and enhance weak unc-16 mutant phenotypes. unc-116 kinesin heavy chain mutants also mislocalize synaptic vesicle markers, as well as a functional UNC-16::GFP. Intriguingly, unc-16 mutations partially suppress the vesicle retention defect in unc-104 KIF1A kinesin mutants. Our results suggest that UNC-16 may regulate the localization of vesicular cargo by integrating JNK signaling and kinesin-1 transport.
    Full-text · Article · Jan 2002 · Neuron
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    ABSTRACT: The C. elegans hermaphrodite gonad is formed by migration of the two distal tip cells (DTC). These cells migrate away from the gonad primordium on the ventral side of the animal (one anterior and the other posterior), turn dorsally and migrate back toward the center of the animal on the dorsal surface resulting in two U-shaped gonad arms of proliferating germ cells (Kimble and White, 1981). We are interested in genes that affect this migratory path and performed a genome-wide RNA interfer-ence (RNAi) screen that revealed 99 genes required for DTC migration (Cram et al., 2006). In this screen, the RNAi-sensitized strain rrf-3(pk1426) was subjected to RNAi by feeding. In this approach, all tissues have the potential to be affected by RNAi; therefore DTC migration might be affected by RNAi knockdown in tissues other than the gonad. To overcome this, we took advantage of the lag-2p::GFP; rde-1(ne219); lag-2p::rde-1 strain of C. elegans (generated by Dr. Dana Byrd and Dr. Judith Kimble) that allows RNAi to have an effect mainly in the two DTCs. We rescreened the 99 genes required for DTC migration with the lag-2p::GFP; rde-1(ne219); lag-2p::rde-1 strain to identify genes that act cell autonomously. We applied the same two step micros-copy approach as Cram et al. (2006), first looking under light microscopy with a dissecting microscope and scoring for worms that show clear patches (intestinal displacement due to gonad abnormal migra-tion or distension). In the second step, we characterized the migratory paths using DIC microscopy and put them into categories (types 1-3) based on gonad morphology. P0 and F1 generations were scored in both screens. The use of the rrf-3(pk1426) sensitized strain resulted in a higher percentage of animals with clear patches in both generations in the primary screen compared to the lag-2p::GFP; rde-1 (ne219); lag-2p::rde-1 strain. Of those adults with clear patches that were analyzed in the secondary screen, the proportions of the three types of DTC migration defects were similar between the two strains. Therefore, whole animal and DTC-specific RNAi give similar DTC migration phenotypes but with different penetrance. Knockdown of 28 of the 99 genes caused DTC migratory defects in 30% or more of the her-maphrodites. Another 31 genes affected DTC migration in 5-29% of adults. Thus, we conclude that these 59 genes have cell autonomous activities during DTC migration. No significant effect on DTC migration was observed in the remaining 40 genes. However, we cannot conclude that these do not act cell autonomously because lack of a defect could result from the less efficient knockdown in the DTC-specific strain.
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Publication Stats

384 Citations
40.58 Total Impact Points


  • 2014
    • San Francisco State University
      • Department of Biology
      San Francisco, California, United States
  • 2006-2012
    • University of Wisconsin, Madison
      • Department of Biochemistry
      Mississippi, United States
  • 2002-2011
    • University of California, Santa Cruz
      Santa Cruz, California, United States