Understanding flagellum formation in mouse spermatozoa

2019 Fiscal Year Annual Research Report

• Project/Area Number: 18K14715
• Research Institution: Osaka University
• Principal Investigator: CASTANEDA JULIO 大阪大学, 微生物病研究所, 特任助教(常勤) (00791659)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: spermatogenesis / flagellum / cilia / sperm motility / fertility / N-DRC

Outline of Annual Research Achievements

My proposal set out the examine cilia and flagella formation by studying 3 components of the Nexin-Dynein Regulatory Complex (N-DRC). The N-DRC is a macromolecular protein complex that helps regulate the beating motion of flagella and cilia as well as their formation. Flagella and cilia are conserved cellular organelles important for cell motility, signaling, embryonic patterning, and organ homeostasis. The N-DRC is composed of 11 subunits (DRC1-11) many of which have been studied in Chlamydomonas, a unicellular green algae. Eight N-DRC components have been studied in mammals leading to various phenotypes such as abnormal organ development (DRC1), short sperm tails (Drc7), immotile sperm (Drc5/Tcte1), or no phenotype at all (Drc6/Fbxl13). The remaining genes yet to be studied include DRC2, 10 (Iqcd), and 11 (Iqca). Using CRISPR/Cas9, I managed to knockout all 3 genes. I found that Drc2 knockout mice are perinatal lethal and exhibit hydrocephalus. Drc11/Iqca mice are fertile with no apparent abnormalities, while Drc10/Iqcd analysis is still ongoing.

Research Products

• [Journal Article] CRISPR/Cas9-based gene knockout in mice uncovers 13 testis- or epididymis-enriched genes individually dispensable for male reproduction (2020)
  • Author(s): Jiang Sun,Yonggang Lu,Kaori Nozawa,Zoulan Xu, Akane Morohoshi,Julio M. Castaneda,Taichi Noda,Haruhiko Miyata, Ferheen Abbasi, Hossam H. Shawki ,Satoru Takahashi,Darius J. Devlin, Zhifeng Yu, Ryan M. Matzuk, Thomas X. Garcia, Martin M. Matzuk, Masahito Ikawa
  • Journal Title: Biology of Reproduction Volume: 102 Pages: 1-9
  • Peer Reviewed / Open Access
• [Journal Article] CIB4 Is Essential for the Haploid Phase of Spermatogenesis in Mice (2020)
  • Author(s): Zoulan Xu, Haruhiko Miyata, Yuki Kaneda, Julio M Castaneda, Yonggang Lu, Akane Morohoshi, Zhifeng Yu, Martin M Matzuk, Masahito Ikawa
  • Journal Title: Biology of Reproduction Volume: 102 Pages: 1-9
  • DOI: 10.1093/biolre/ioaa059
  • Peer Reviewed / Open Access
• [Journal Article] Tesmin, Metallothionein-Like 5, Is Required for Spermatogenesis in Mice (2020)
  • Author(s): Asami Oji, Ayako Isotani, Yoshitaka Fujihara, Julio M Castaneda, Seiya Oura, Masahito Ikawa
  • Journal Title: Biology of Reproduction Volume: 102 Pages: 975-983
  • DOI: 10.1093/biolre/ioaa002
  • Peer Reviewed / Open Access
• [Journal Article] Mouse T-Complex Protein 11 Is Important for Progressive Motility in Sperm (2019)
  • Author(s): Julio M Castaneda, Haruhiko Miyata, Denise R Archambeault, Yuhkoh Satouh, Zhifeng Yu, Masahito Ikawa, Martin M Matzuk
  • Journal Title: Biology of Reproduction Volume: 102 Pages: 852-862
  • DOI: 10.1093/biolre/ioz226
  • Peer Reviewed / Open Access
• [Journal Article] CRISPR/Cas9-mediated Genome Editing Reveals 30 Testis-Enriched Genes Dispensable for Male Fertility in Mice (2019)
  • Author(s): Y Lu, S Oura, T Matsumura, A Oji, N Sakurai, Y Fujihara, K Shimada, H Miyata, T Tobita, T Noda, J M Castaneda, D Kiyozumi, Q Zhang, T Larasati, S A M Young, M Kodani, C A Huddleston, M J Robertson, C Coarfa, A Isotani, R J Aitken, M Okabe, M M Matzuk, T X Garcia, M Ikawa
  • Journal Title: Biology of Reproduction Volume: 101 Pages: 501-511
  • DOI: 10.1093/biolre/ioz103
  • Peer Reviewed / Open Access
• [Presentation] Spar1 is a novel transmembrane gene required for acrosome formation in mice (2019)
  • Author(s): Julio M Castaneda
  • Organizer: Society for the Study of Reproduction
  • Int'l Joint Research