Gumienny TL et al. (2013) WormBook "TGF- signaling in C. elegans."

Savage-Dunn C, Gumienny TL

[WormBook, 2013]

Transforming Growth Factor- (TGF-) superfamily ligands regulate many aspects of cell identity, function, and survival in multicellular animals. Genes encoding five TGF- family members are present in the genome of C. elegans. Two of the ligands, DBL-1 and DAF-7, signal through a canonical receptor-Smad signaling pathway; while a third ligand, UNC-129, interacts with a noncanonical signaling pathway. No function has yet been associated with the remaining two ligands. Here we summarize these signaling pathways and their biological functions.

Gumienny TL et al. (2003) Bioessays "A small issue addressed."

Padgett RW, Gumienny TL

[Bioessays, 2003]

Cell size is an important determinant of body size. While the genetic mechanisms of cell size regulation have been well studied in yeast, this process has only recently been addressed in multicellular organisms. One recent report by Wang et al. (2002) shows that in the nematode C. elegans, the TGFbeta-like pathway acts in the hypodermis to regulate cell size and consequently body size.((1)) This finding is an exciting step in discovering the molecular mechanisms that control cell and body size.

Gumienny TL et al. (1995) International C. elegans Meeting "PROGRAMMED CELL DEATH IN THE GERMLINE"

Hartweig EA, Horvitz HR, Gumienny TL, Hengartner MO

[International C. elegans Meeting, 1995]

Germ cells in C. elegans can either remain mitotic stem cells or enter meiosis and undergo spermatogenesis or oogenesis. We are exploring observations of another germ cell fate: programmed cell death (PCD). Our results suggest that PCD occurs extensively in the germ line as a part of or as a by-product of oogenesis. Most mutations that affect PCD in the soma also affect germ cell deaths. ced-9, shown to be necessary to protect cells that should live from dying, is also required in the germ line; many more germ cells undergo PCD in ced-9(lf) mutants than in N2 animals, which may explain the partial sterility of ced-9(lf) mutants. However, the gain-of-function mutation ced-9(n1950), while blocking somatic cell deaths entirely, has little or no effect on germ cell deaths. ced-3 and ced-4, necessary for somatic cell deaths, are also required for germ cell deaths; we found no corpses in the germline of ced-3 or ced-4 mutants. Mutations in the engulfment genes ced-1, -2, -5, -6, -7, and -10, which prevent efficient engulfment of dying somatic cells by adjacent cells, also obstruct engulfment of dying germ cells by the somatic sheath cells. From the number of accumulated germ cell corpses in these mutants, we estimate that over a third of all possible oocytes undergo PCD. The germ cells function as nurse cells before becoming oocytes. We suggest that the number of nurse cells generated exceeds the number of oocytes that can be accommodated, and that the superfluent nurse cells are removed through PCD. As evidence, we see corpses in the meiotic part of the gonad soon after oogenesis begins, but identify few to no corpses in larvae and males. We are currently screening for suppressors of PCD in the gonad using a ced-1 engulfment mutant. Mutants should suppress cell death and thereby reduce the number of corpses retained in the gonad.

Gumienny, T.L. et al. (2017) International Worm Meeting "TWU Active Engagement Academy: Improving active engagement in academic courses."

Gumienny, T.L., Westmoreland , S.

[International Worm Meeting, 2017]

High enrollment classes (>50 students) have historically been associated with lower student engagement and higher failure rates than lower enrollment classes. Active learning has been demonstrated to increase student engagement and, indirectly, student persistence. In addition, faculty who use high engagement in their classrooms become pedagogical role models for the future teachers who are enrolled in their courses. By initiating an Active Engagement Academy at Texas Woman's University, faculty who teach large lecture classes have been recruited and trained to use active learning and teaching methods to foster student engagement, academic success, and retention. The Active Engagement Academy model will be self-perpetuating as participating faculty will become role models within their academic departments for other faculty and for the teacher candidates enrolled in their courses. This presentation will provide a model and framework for other instructors who wish to promote active engagement in their institution's classrooms, including the rationale, recruiting information, workshop plans, and designs for active engagement implementations and measurements for intervention success.

Gumienny TL et al. (1999) Development "Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline."

Horvitz HR, Hengartner MO, Gumienny TL, Hartweig EA, Lambie EJ

[Development, 1999]

Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths. However, this machinery is activated by a distinct pathway, as loss of egl-1 function, which inhibits somatic cell death, does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway activation and is used to maintain germline homeostasis. We suggest that apoptosis eliminates excess germ cells that acted as nurse cells to provide cytoplasmic components to maturing oocytes.

Gumienny TL et al. (1998) East Coast Worm Meeting "FURTHER STUDIES OF PROGRAMMED CELL DEATH IN THE GERMLINE"

Hengartner MO, Lambie EJ, Gumienny TL

[East Coast Worm Meeting, 1998]

Germ cells in C. elegans can either remain mitotic stem cells or enter meiosis and undergo spermatogenesis or oogenesis. We have previously reported that germ cells can also undergo programmed cell death (PCD). PCD occurs extensively in the germ line as a part of or as a by-product of oogenesis, and requires the known cell death genes. Loss-of-function mutations in the cell death repressor gene ced-9 cause excess germ cell death, while mutations in cell killer genes ced-3 and ced-4 prevent germ cell death. The genes involved in engulfment and nuc-1 are also required to remove and degrade germ cell deaths. Known cell-specific cell death regulators have no apparent effect on germ cell death. The germ cells function as nurse cells before becoming oocytes. We suggest that the number of nurse cells generated exceeds the number of oocytes that can be accommodated, and that the superfluous nurse cells are removed through PCD. If cell death is blocked (as in ced-3(lf) and ced-4(lf) animals), then the syncytium expands in older animals to accommodate the extra germ nuclei. We have found that germ cell death is prevented by mutations in the Ras pathway that block meiotic cell cycle progression beyond pachytene. However, pachytene-arrested cells have the capacity to die, but are prevented from doing so through a ced-9-dependent mechanism. This finding suggests that activation of the Ras pathway may allow progression of germ cells from an early, cell-death resistant stage, to a later, cell-death sensitive stage of meiosis.

Gumienny TL et al. (1997) International C. elegans Meeting "CHARACTERIZATION AND CLONING OF A NOVEL ENGULFMENT GENE, ced(oz167)"

Francis R, Hengartner MO, Gumienny TL, Schedl TB

[International C. elegans Meeting, 1997]

Rapid recognition and removal of dying cells are important and conserved components of all apoptotic death programs. In mammalian systems, a defect in cell death removal may result in arthritis and other inflammatory diseases. In C. elegans, loss of function of any one of the six previously identified genes (ced-1, -2, -5, -6, -7, and -10) results in cell deaths that persist for several hours (Ellis, 1991). We are characterizing and attempting to clone a novel engulfment gene based on a single mutation, ced(oz167). ced(oz167) is a recessive mutation. Like mutations in all other engulfment genes except ced-1, ced(oz167) is maternally rescued in the embryo but not in the adult germline. We have previously shown that the engulfment genes fall into two groups. The first comprises genes with a largely engulfment-specific phenotype (ced-1, ced-6, and ced-7), and the second includes genes with pleiotropic effects (ced-2, ced-5, and ced-10), including, most notably, a distal tip cell migration defect. ced(oz167) is a member of the latter class, exhibiting not only a strong persistent cell death phenotype, but also pleiotropies displayed by other mutations in its class. The engulfment defect is suppressed by ced-3 and ced-4, but the DTC migration defect remains, suggesting ced(oz167)'s involvement in multiple roles. We have tentatively mapped ced(oz167) between mec-8 and lin-11 on LGI. The status of cloning oz167 will be presented. Ellis et al. (1991). Genetics 129: 79-94.

Gumienny TL et al. (2001) Cell "CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration."

Haney LB, Gumienny TL, Brugnera E, Francis R, Nemergut ME, Tosello-Trampont AC, Hengartner MO, Macara IG, Schedl T, Qin Y, Kinchen JM, Ravichandran KS, Van Aelst L, Nishiwaki K, Walk SF

[Cell, 2001]

The C. elegans genes ced-2, ced-5, and ced-10, and their mammalian homologs crkII, dock180, and rac1, mediate cytoskeletal rearrangements during phagocytosis of apoptotic cells and cell motility. Here, we describe an additional member of this signaling pathway, ced-12, and its mammalian homologs, elmo1 and elmo2. In C. elegans, CED-12 is required for engulfment of dying cells and for cell migrations. In mammalian cells, ELMO1 functionally cooperates with CrkII and Dock180 to promote phagocytosis and cell shape changes. CED-12/ELMO-1 binds directly to CED-5/ Dock180; this evolutionarily conserved complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal rearrangements. These studies identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and cell migration from C. elegans to mammals.

Gumienny TL et al. (2007) Curr Biol "Glypican LON-2 is a conserved negative regulator of BMP-like signaling in Caenorhabditis elegans."

MacNeil LT, Gumienny TL, Padgett RW, Wrana JL, Wang H, De Bono M

[Curr Biol, 2007]

Bone morphogenetic protein (BMP) pathways are required for a wide variety of developmental and homeostatic decisions, and mutations in signaling components are associated with several diseases. An important aspect of BMP control is the extracellular regulation of these pathways. We show that LON-2 negatively regulates a BMP-like signaling pathway that controls body length in C. elegans. lon-2 acts genetically upstream of the BMP-like gene dbl-1, and loss of lon-2 function results in animals that are longer than normal. LON-2 is a conserved member of the glypican family of heparan sulfate proteoglycans, a family with several members known to regulate growth-factor signaling in many organisms. LON-2 is functionally conserved because the Drosophila glypican gene dally rescues the lon-2(lf) body-size defect. We show that the LON-2 protein binds BMP2 in vitro, and a mutant variation of LON-2 found in lon-2(e2140) animals diminishes this interaction. We propose that LON-2 binding to DBL-1 negatively regulates this pathway in C. elegans by attenuating ligand-receptor interactions. This is the first report of a glypican directly interacting with a growth-factor pathway in C. elegans and provides a mechanistic model for glypican regulation of growth-factor pathways.

Gumienny TL et al. (2010) PLoS Genet "Caenorhabditis elegans SMA-10/LRIG is a conserved transmembrane protein that enhances bone morphogenetic protein signaling."

Wrana JL, MacNeil L, Wang H, Padgett RW, Zimmerman CM, Chin L, Gumienny TL

[PLoS Genet, 2010]

Bone morphogenetic protein (BMP) pathways control an array of developmental and homeostatic events, and must themselves be exquisitely controlled. Here, we identify Caenorhabditis elegans SMA-10 as a positive extracellular regulator of BMP-like receptor signaling. SMA-10 acts genetically in a BMP-like (Sma/Mab) pathway between the ligand DBL-1 and its receptors SMA-6 and DAF-4. We cloned sma-10 and show that it has fifteen leucine-rich repeats and three immunoglobulin-like domains, hallmarks of an LRIG subfamily of transmembrane proteins. SMA-10 is required in the hypodermis, where the core Sma/Mab signaling components function. We demonstrate functional conservation of LRIGs by rescuing sma-10(lf) animals with the Drosophila ortholog lambik, showing that SMA-10 physically binds the DBL-1 receptors SMA-6 and DAF-4 and enhances signaling in vitro. This interaction is evolutionarily conserved, evidenced by LRIG1 binding to vertebrate receptors. We propose a new role for LRIG family members: the positive regulation of BMP signaling by binding both Type I and Type II receptors.