title: A novel transcriptional factor Nkapl is a germ cell-specific suppressor of Notch signaling and is indispensable for spermatogenesis.
abstract: Spermatogenesis is an elaborately regulated system dedicated to the continuous production of spermatozoa via the genesis of spermatogonia. In this process, a variety of genes are expressed that are relevant to the differentiation of germ cells at each stage. Although Notch signaling plays a critical role in germ cell development in Drosophila and Caenorhabditis elegans, its function and importance for spermatogenesis in mammals is controversial. We report that Nkapl is a novel germ cell-specific transcriptional suppressor in Notch signaling. It is also associated with several molecules of the Notch corepressor complex such as CIR, HDAC3, and CSL. It was expressed robustly in spermatogonia and early spermatocytes after the age of 3 weeks. Nkapl-deleted mice showed complete arrest at the level of pachytene spermatocytes. In addition, apoptosis was observed in this cell type. Overexpression of NKAPL in germline stem cells demonstrated that Nkapl induced changes in spermatogonial stem cell (SSC) markers and the reduction of differentiation factors through the Notch signaling pathway, whereas testes with Nkapl deleted showed inverse changes in those markers and factors. Therefore, Nkapl is indispensable because aberrantly elevated Notch signaling has negative effects on spermatogenesis, affecting SSC maintenance and differentiation factors. Notch signaling should be properly regulated through the transcriptional factor Nkapl.
authors: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Hidenobu
authors: H
authors: Okuda
authors: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Hiroshi
authors: H
authors: Kiuchi
authors: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Tetsuya
authors: T
authors: Takao
authors: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Yasushi
authors: Y
authors: Miyagawa
authors: Department of Urology, Juntendo University Hospital, Tokyo, Japan.
authors: Akira
authors: A
authors: Tsujimura
authors: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Norio
authors: N
authors: Nonomura
authors: Animal Resource Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors: Haruhiko
authors: H
authors: Miyata
authors: Animal Resource Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors: Masaru
authors: M
authors: Okabe
authors: Animal Resource Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors: Masahito
authors: M
authors: Ikawa
authors: National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
authors: Yoshitaka
authors: Y
authors: Kawakami
authors: National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
authors: Naoki
authors: N
authors: Goshima
authors: Molecular Biology Division, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki, Japan.
authors: Morimasa
authors: M
authors: Wada
authors: Molecular Biology Division, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki, Japan.
authors: Hiromitsu
authors: H
authors: Tanaka
mesh_terms: D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D000072056:Transcription Factor HES-1; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D056970:Co-Repressor Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C489685:Hes5 protein, mouse; C569368:NKAPL protein, human