Understanding flagellum formation in mouse spermatozoa

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14715
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• 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 / sperm / N-DRC / sperm motility / male fertility / hydrocephalus

Outline of Final 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 important for cell and organ function. The N-DRC is composed of 11 subunits (DRC1-11). Eight N-DRC components have been studied in the mouse that lead 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.

Free Research Field

Developmental Biology

Academic Significance and Societal Importance of the Research Achievements

The N-DRC is an important macromolecular complex that help regulate flagella and cilia formation and function. My research examined the last remaining components of the N-DRC that have yet to be studied. This research completes the analysis of all components of the N-DRC.