Find in Library

CRISPR/Cas9 system has opened a new era for reverse genetics. Taking advantage of the CRISPR/Cas9-mediated approaches, our laboratory has knocked out 421 male reproductive organ-specific genes and analysed their phenotypes in vivo. Surprisingly, even with the highly testis-specific genes (TPM>10 and 10 times higher expression than any other non-reproductive tissues), only one-third is individually essential for male fertility (37/120=30.8%), suggesting that the tissue-specific expression does not necessarily mean essential for physiological functions (1). Nevertheless, this KO screening approach has allowed us to identify 116 genes essential for male reproductive function. Among them, we recently elucidated the long-sought lumicrine system. Testicular NELL2/NICOL goes through the efferent duct’s lumen and stimulates the ROS1 signalling pathway in the epididymal epithelial cells. Thus, differentiated epididymal epithelial cells secrete proteases such as OVCH2 that mediate sperm ADAM3 trimming and sperm maturation (2-3). Finally, I would like to introduce recent findings on the molecular mechanism of mammalian fertilization (4-6 ).