C. elegans projects

Cell division is one of the most fundamental processes of life, and the core molecular mechanisms that guide cells through the cellular events of growth, DNA replication, and division into two daughter cells are evolutionarily conserved from yeast to humans.  However while we now understand the basics of this core program, we know much less about the ways that the core cycle is modified and regulated by cell specific factors. In the Shakes’ lab we are exploring the following question…

How is the meiotic cell cycle that gives rise to sperm and oocytes coordinated with the distinct developmental programs that give rise to either large, nutrient rich oocytes or small, motile sperm?

• Winter ES, Schwarz A, Fabig G, Feldman JL, Pires-daSilva A, Müller-Reichert T, Sadler PL, Shakes DC. Cytoskeletal variations in an asymmetric cell division support diversity in nematode sperm size and sex ratios. Development. 2017 Sep 15;144(18):3253-3263.
• Shakes DC, Wu JC, Sadler PL, Laprade K, Moore LL, Noritake A, Chu DS. Spermatogenesis-specific features of the meiotic program in Caenorhabditis elegans. PLoS Genet. 2009 Aug;5(8):e1000611. doi: 10.1371/journal.pgen.1000611.
• Shakes DC, Sadler PL, Schumacher JM, Abdolrasulnia M, Golden A. Developmental defects observed in hypomorphic anaphase-promoting complex mutants are linked to cell cycle abnormalities. Development. 2003 Apr;130(8):1605-20. doi: 10.1242/dev.00385.

By design, sperm cells are small, motile, and transcriptionally inactive. Thus a key step in the developmental program of making a sperm involves prepackaging components that need to be synthesized before the turnoff of transcription and stored for later use. Nematode spermatogenesis provides an extreme example of this process; bulk transcription ceases prior to the meiotic divisions and translation ceases immediately after anaphase II. In particular, spermatocytes must synthesize and prepackage a small filament forming protein called the major sperm protein (MSP). Within mature nematode sperm, MSP serves both as the protein that drives sperm motility and as a signaling protein that triggers oocyte maturation and the physical process of ovulation. Some of the questions that we are currently exploring include…

Once a germ cell has committed to being a spermatocyte rather than an oocyte, what transcription factors and post-translational modifiers implement the spermatogenesis program – and make sure that the “roll-out” is successful?

• Ragle JM, Morrison KN*, Vo AA, Johnson ZE, Lopez JH, Rechtsteiner A, Shakes DC, and Ward JD (2022) NHR-23 and SPE-44 regulate distinct sets of genes during C. elegans spermatogenesis. G3 Genes/Genomes/Genetics. https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkac256/6711396
• Ragle JM, Aita AL, Morrison KN, Martinez-Mendez R, Saeger HN, Ashley GA, Johnson LC, Schubert KA, Shakes DC, Ward JD. The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis. Development. 2020 Nov 27;147(22):dev193862. doi: 10.1242/dev.193862.
• Peterson JJ, Tocheny CE, Prajapati G, LaMunyon CW, Shakes DC. Subcellular patterns of SPE-6 localization reveal unexpected complexities in Caenorhabditis elegans sperm activation and sperm function. G3 (Bethesda). 2021 Oct 19;11(11):jkab288. doi: 10.1093/g3journal/jkab288.
• Kulkarni M, Shakes DC, Guevel K, Smith HE. SPE-44 implements sperm cell fate. PLoS Genet. 2012;8(4):e1002678. doi: 10.1371/journal.pgen.1002678.

How is it that the major sperm protein (MSP) can assemble into large stable fibrous bodies within spermatocytes but later undergo dynamic polymerization within the pseudopods of crawling spermatozoa?

• Price KL, Presler M, Uyehara CM, Shakes DC. The intrinsically disordered protein SPE-18 promotes localized assembly of MSP in Caenorhabditis elegans spermatocytes. Development. 2021 Mar 5;148(5):dev195875. doi: 10.1242/dev.195875.