title: R-spondin 1/dickkopf-1/beta-catenin machinery is involved in testicular embryonic angiogenesis.
abstract: Testicular vasculogenesis is one of the key processes regulating male gonad morphogenesis. The knowledge of the molecular cues underlining this phenomenon is one of today's most challenging issues and could represent a major contribution toward a better understanding of the onset of testicular morphogenetic disorders. R-spondin 1 has been clearly established as a candidate for mammalian ovary determination. Conversely, very little information is available on the expression and role of R-spondin 1 during testicular morphogenesis. This study aims to clarify the distribution pattern of R-spondin 1 and other partners of its machinery during the entire period of testicular morphogenesis and to indicate the role of this system in testicular development. Our whole mount immunofluorescence results clearly demonstrate that R-spondin 1 is always detectable in the testicular coelomic partition, where testicular vasculature is organized, while Dickkopf-1 is never detectable in this area. Moreover, organ culture experiments of embryonic male UGRs demonstrated that Dickkopf-1 acted as an inhibitor of testis vasculature formation. Consistent with this observation, real-time PCR analyses demonstrated that DKK1 is able to slightly but significantly decrease the expression level of the endothelial marker Pecam1. The latter experiments allowed us to observe that DKK1 administration also perturbs the expression level of the Pdgf-b chain, which is consistent with some authors' observations relating this factor with prenatal testicular patterning and angiogenesis. Interestingly, the DKK1 induced inhibition of testicular angiogenesis was rescued by the co-administration of R-spondin 1. In addition, R-spondin 1 alone was sufficient to enhance, in culture, testicular angiogenesis.
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics-Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Caruso
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics-Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy; Italian Space Agency, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferranti
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics-Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Corano Scheri
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics-Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy; Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Dobrowolny
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciccarone
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics-Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Catizone
authors.affiliation: Department of Experimental Medicine-Histology and Embryology Laboratory, Second University of Naples, Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ricci
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D009024:Morphogenesis / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000196:embryology* / Q000378:metabolism*; D019699:Thrombospondins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C496200:LGR4 protein, mouse; C518903:RSPO1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D019699:Thrombospondins; D051176:beta Catenin