Kwah, Ji Kent et al. (2021) International Worm Meeting "Role of spe-11 and oops-1 in early embryogenesis and eggshell formation"

Jaramillio-Lambert, Aimee, Tsukamoto, Tatsuya, Kwah, Ji Kent, Greenstein, David

[International Worm Meeting, 2021]

Gametes provide a variety of cellular and genetic materials during their fusion to form a zygote. Although the majority of proteins required for embryogenesis are maternally provided and present in the oocyte, sperm contributions are also essential to this process. In the model organism C. elegans, SPE-11 is a sperm protein identified to be paternal-effect embryonic lethal. It was experimentally shown that homozygous mutant sperm (from hermaphrodite or male) will always lead to non-viable embryos regardless of the source of oocyte. However, oocytes from a spe-11 mutant can be successfully fertilized when sperm from a wild type male is provided therefore confirming SPE-11 function can only be provided by the paternal gamete. spe-11 mutant single cell embryos are defective in a myriad of ways such as inability to complete the meiotic divisions and cytokinesis, improper spindle formation, and weak eggshell formation. Currently, little is known about the role and function of the SPE-11 protein as it has no known homology to any known domains. Recently, an interacting partner of SPE-11 was identified and given the name oocyte partner of SPE-11 (OOPS-1). As these two proteins were found to physically interact, we asked if mutant versions had similar phenotypes. Similar to spe-11 mutants, we found that deletion mutants of oops-1 are embryonic lethal indicating that the OOPS-1 protein is required for the embryogenesis process. We are using fluorescently labeled histones and meiotic spindles to image oocyte meiosis in vivo in wild-type, spe-11(hc90), and oops-1(tn1898) strains. Interestingly, while both spe-11 and oops-1 mutants have defects in oocyte meiosis, the two mutants have slightly different phenotypes. As previously published, in spe-11(hc90) mutant embryos, the chromosomes segregate at anaphase I and II but fail to form polar bodies. In contrast, it appears that oops-1(tn1898) can complete meiosis I but cannot enter anaphase II. The exact timing and the analysis of other meiotic division phenotypes is still ongoing. Alongside this, we are also investigating the integrity of the embryo eggshell in these mutants.

Snyder, Matthew P. et al. (2013) International Worm Meeting "Turnover of the H3K9me2 Mark During Late Spermatogenesis."

Snyder, Matthew P., Xu, Xia, Maine, Eleanor

[International Worm Meeting, 2013]

Meiotic silencing is a conserved phenomenon targeting unpaired chromosomes and chromosomal regions during prophase of meiosis I. Meiotic silencing in animals typically occurs at the chromatin level and involves accumulation of histone modifications thought to promote a closed chromatin configuration. This chromatin structure may contribute to transcriptional repression and meiotic chromosomal events such as chromosome disjunction (Bean et al 2004, Jaramillo-Lambert and Engebrecht 2010). During meiosis in C. elegans, non-synapsed chromosomes are enriched for H3K9me2 relative to synapsed chromosomes (Kelly et al. 2002; Bean et al. 2004). Such non-synapsed chromosomes include the male X, homologous chromosomes that fail to synapse due to mutation, and chromosomal translocations/duplications. The pattern of H3K9me2 accumulation during meiosis depends on activity of the small RNA machinery, which may have a role in targeting the mark to unpaired chromosomes and ensuring that the mark does not persist abnormally (Maine et al. 2005; She et al. 2009). Taking a combined biochemical/genetic approach, we are identifying additional factors important for regulating H3K9me2 distribution during meiosis. Through this approach, we are identifying genes that appear to be important for turnover of the H3K9me2 mark during late spermatogenesis.

Sandrine Fraboulet et al. (2009) European Worm Neurobiology Meeting "Chemical rescue of paralysis in a transgenic model of Caenorhabditis elegans overexpressing human Beta-amyloid"

David I C Scopes, Andrew K Jones, David B Sattelle, Aileen Moloney, Christopher D Link, Steven D Buckingham, Mark J Treherne, Hozefa Amijee, Sandrine Fraboulet

[European Worm Neurobiology Meeting, 2009]

Authors acknowledge support from MRC. Numerous studies support a role for aggregated Ab as a mediator of the toxicity that underlies Alzheimer.s disease (AD) and other diseases such as Inclusion Body myositis (IBM), an acquired muscle disease affecting people over 50 years old. In this pathology, muscle weakness and degeneration is accompanied by chronic muscle inflammation. Remarkably, despite the inflammation component of the disease, IBM patients are only poorly responsive to anti-inflammatory drugs suggesting that inflammation per se may not be the primary cause of the pathology. We have used a C. elegans transgenic line over-expressing human amyloid 1-42 peptide in the muscles as a model with which to test the efficiency of new compounds on in vivo amyloid toxicity. This C. elegans line becomes paralyzed shortly after the induction of amyloid expression in the muscles, which makes it an easily-recordable phenotype useful for exploring candidate treatments to alleviate the paralysis. We report on the actions of two novel chemicals, which inhibit amyloid aggregation and partially rescue the amyloid-induced phenotype. References: Wu Y, W.Z., Butko P, Christen Y, Lambert MP, Klein WL, Link CD, Luo Y. (2006) J. Neurosci., 26, 13102-13. Link CD, T.A., Kapulkin V, Duke K, Kim S, Fei Q, Wood DE, Sahagan BG. (2003) Neurobiol Aging., 24, 397-413. Jones, A.K., Buckingham, S.D. and Sattelle, D.B. (2005). Nat Rev Drug Discov, 4, 321-30.

Gong, Ting et al. (2021) International Worm Meeting "C. elegans maximize the number of euploid progeny from zim-2 parents with crossover failure on chromosome V."

Gong, Ting, McNally, Francis, Tran, Thuy-Linh

[International Worm Meeting, 2021]

Gametes with incorrect chromosome number can lead to embryonic lethality and developmental deficiency if inherited. Parental trisomy or crossover failure are two conditions expected to yield random meiotic segregation and 25% trisomy among offspring. We previously demonstrated that parental trisomy of the X can be corrected among progeny by preferentially placing the extra chromosome in the first polar body (Cortes, eLife.06056). If 100% efficient, such a univalent elimination mechanism would generate 100% lethal monosomy among progeny of parents with crossover failure. However, high viability rates have been reported among progeny of him-8 mutants (crossover failure on X) (Hodgkin, Genetics 91:67), zim-2 mutants (crossover failure on V) and zim-1 mutants (crossover failure on II and III) (Jaramillo-Lambert, Curr Biol 20:2078), suggesting the possible existence of a distributive segregation mechanism that is more efficient during spermatogenesis than during oogenesis. Here we directly measured the frequency of monosomy, disomy and trisomy among the progeny of zim-1 mutants and zim-2 mutants mated to wild type using PCR polymorphisms that differ between three strain backgrounds. Zim-1 hermaphrodites mated to wild-type males produced 72% disomy II progeny (n=33) and 57% disomy III progeny (n=54). This difference from the 50% expected from random segregation was not significant. Zim-2 hermaphrodites mated with wild-type males produced 73% disomy V progeny (n=65) which was not significantly different than random segregation when corrected for 24% (n=42) crossovers on V observed by counting diakinesis bivalents in oocytes. In striking contrast, zim-2 males mated to wild-type hermaphrodites produced 95% disomy V progeny (n=94) which is significantly higher than random segregation. We are currently testing whether this is due to a high frequency of crossovers on V in zim-2 males, more efficient fertilization by euploid sperm, or a genuine distributive segregation system during male meiosis. A side benefit of our approach is that we can determine the phenotypes of most single chromosome aneuploidies. We have thus far observed monosomies of II, III, or V only in dead embryos and have observed trisomies of II, III, or V only among hatched larvae.