Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-9-17
pubmed:abstractText
The first morphological sign of testicular differentiation is the formation of testis cords. Prior to cord formation, newly specified Sertoli cells establish adhesive junctions, and condensation of somatic cells along the surface epithelium of the genital ridge occurs. Here, we show that Sertoli cell aggregation is necessary for subsequent testis cord formation, and that neurotrophic tyrosine kinase receptors (NTRKs) regulate this process. In a three-dimensional cell culture assay, immature rat Sertoli cells aggregate to form large spherical aggregates (81.36+/-7.34 microm in diameter) in a highly organized, hexagonal arrangement (376.95+/-21.93 microm average distance between spherical aggregates). Exposure to NTRK inhibitors K252a and AG879 significantly disrupted Sertoli cell aggregation in a dose-dependent manner. Sertoli cells were prevented from establishing cell-cell contacts and from forming spherical aggregates. In vitro-derived spherical aggregates were xenografted into immunodeficient nude mice to investigate their developmental potential. In controls, seminiferous tubule-like structures showing polarized single-layered Sertoli cell epithelia, basement membranes, peritubular myoid cells surrounding the tubules, and lumen were observed in histological sections. By contrast, grafts from treatment groups were devoid of tubules and only few single Sertoli cells were present in xenografts after 4 weeks. Furthermore, the grafts were significantly smaller when Sertoli cell aggregation was disrupted by K252a in vitro (20.87 vs 6.63 mg; P<0.05). We conclude from these results that NTRK-regulated Sertoli-Sertoli cell contact is essential to the period of extensive growth and remodeling that occurs during testicular tubulogenesis, and our data indicate its potential function in fetal and prepubertal testis differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1741-7899
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
136
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
459-69
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18660385-Animals, pubmed-meshheading:18660385-Carbazoles, pubmed-meshheading:18660385-Cell Aggregation, pubmed-meshheading:18660385-Cell Communication, pubmed-meshheading:18660385-Cell Culture Techniques, pubmed-meshheading:18660385-Dose-Response Relationship, Drug, pubmed-meshheading:18660385-Indole Alkaloids, pubmed-meshheading:18660385-Male, pubmed-meshheading:18660385-Mice, pubmed-meshheading:18660385-Mice, Nude, pubmed-meshheading:18660385-Morphogenesis, pubmed-meshheading:18660385-Rats, pubmed-meshheading:18660385-Rats, Inbred Strains, pubmed-meshheading:18660385-Receptor, trkA, pubmed-meshheading:18660385-Seminiferous Tubules, pubmed-meshheading:18660385-Sertoli Cells, pubmed-meshheading:18660385-Testis, pubmed-meshheading:18660385-Transplantation, Heterologous, pubmed-meshheading:18660385-Tyrphostins
pubmed:year
2008
pubmed:articleTitle
Initiation of testicular tubulogenesis is controlled by neurotrophic tyrosine receptor kinases in a three-dimensional Sertoli cell aggregation assay.
pubmed:affiliation
Department of Cell Biology and Physiology, Center for Research in Reproductive Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural