title: Cell context-specific expression of primary cilia in the human testis and ciliary coordination of Hedgehog signalling in mouse Leydig cells.
abstract: Primary cilia are sensory organelles that coordinate numerous cellular signalling pathways during development and adulthood. Defects in ciliary assembly or function lead to a series of developmental disorders and diseases commonly referred to as ciliopathies. Still, little is known about the formation and function of primary cilia in the mammalian testis. Here, we characterized primary cilia in adult human testis and report a constitutive expression of cilia in peritubular myoid cells and a dynamic expression of cilia in differentiating Leydig cells. Primary cilia are generally absent from cells of mature seminiferous epithelium, but present in Sertoli cell-only tubules in Klinefelter syndrome testis. Peritubular cells in atrophic testis produce overly long cilia. Furthermore cultures of growth-arrested immature mouse Leydig cells express primary cilia that are enriched in components of Hedgehog signalling, including Smoothened, Patched-1, and GLI2, which are involved in regulating Leydig cell differentiation. Stimulation of Hedgehog signalling increases the localization of Smoothened to the cilium, which is followed by transactivation of the Hedgehog target genes, Gli1 and Ptch1. Our findings provide new information on the spatiotemporal formation of primary cilia in the testis and show that primary cilia in immature Leydig cells mediate Hedgehog signalling.
authors.affiliation: 1] University Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Copenhagen DK-2100, Denmark [2] Department of Biology, University of Copenhagen, Copenhagen DK-2100, Denmark.
authors.forename: Marie Berg
authors.initials: MB
authors.lastname: Nygaard
authors.affiliation: University Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Copenhagen DK-2100, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Almstrup
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen DK-2100, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Lindbæk
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen DK-2100, Denmark.
authors.forename: Søren Tvorup
authors.initials: ST
authors.lastname: Christensen
authors.affiliation: 1] University Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Copenhagen DK-2100, Denmark [2] Department of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Søborg DK-2860, Denmark.
authors.forename: Terje
authors.initials: T
authors.lastname: Svingen
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007713:Klinefelter Syndrome / Q000378:metabolism / Q000473:pathology; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D013737:Testis / Q000378:metabolism*; D000075746:Zinc Finger Protein Gli2
chemical_list: C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D000075746:Zinc Finger Protein Gli2