Linked Life Data

21147849

Source:http://linkedlifedata.com/resource/pubmed/id/21147849

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-3
pubmed:abstractText
During male development, the testes move from a high intraabdominal position and descend into the scrotum. The gubernaculum, an inguinoscrotal ligament connecting the testis to the lower abdomen, is believed to play a critical role in this process. The first stage of testicular descent is controlled by insulin like3 hormone (INSL3), produced in testicular Leydig cells. Deletion of Insl3 or its receptor, Rxfp2, in mice causes cryptorchidism. We produced Cre/loxP regulated shRNA transgenic mice targeting RXFP2 expression. We have shown that the transgene was able to reduce Rxfp2 gene expression and thus behaved as a hypomorphic allele of Rxfp2. Variable degrees of uni- and bilateral cryptorchidism was detected in males with the activated shRNA transgene on an Rxfp2+/- background. Conditional suppression of Rxfp2 in the gubernaculum led to cryptorchidism. Gene expression analysis of a mutant cremasteric sac using Illumina microarrays indicated abnormal expression of a significant number of genes in Wnt/?-catenin and Notch pathways. We have demonstrated profound changes in the expression pattern of ?-catenin, Notch1, desmin, and androgen receptor (AR), in Rxfp2-/- male embryos, indicating the role of INSL3 in proliferation, differentiation, and survival of specific cellular components of the gubernaculum. We have shown that INSL3/RXFP2 signaling is essential for myogenic differentiation and maintenance of AR-positive cells in the gubernaculum. Males with the deletion of ?-catenin or Notch1 in the gubernacular ligament demonstrated abnormal development. Our data indicates that ?-catenin and Notch pathways are potential targets of INSL3 signaling during gubernacular development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1944-9917
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
170-83
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21147849-Animals, pubmed-meshheading:21147849-Cell Differentiation, pubmed-meshheading:21147849-Cryptorchidism, pubmed-meshheading:21147849-Gene Deletion, pubmed-meshheading:21147849-Gene Expression Regulation, Developmental, pubmed-meshheading:21147849-HEK293 Cells, pubmed-meshheading:21147849-Humans, pubmed-meshheading:21147849-Insulin, pubmed-meshheading:21147849-Ligaments, pubmed-meshheading:21147849-Male, pubmed-meshheading:21147849-Mice, pubmed-meshheading:21147849-Models, Biological, pubmed-meshheading:21147849-Muscle Development, pubmed-meshheading:21147849-Proteins, pubmed-meshheading:21147849-RNA, Small Interfering, pubmed-meshheading:21147849-Receptors, Androgen, pubmed-meshheading:21147849-Receptors, G-Protein-Coupled, pubmed-meshheading:21147849-Receptors, Notch, pubmed-meshheading:21147849-Signal Transduction, pubmed-meshheading:21147849-Transgenes, pubmed-meshheading:21147849-beta Catenin
pubmed:year
2011
pubmed:articleTitle
Suppression of insulin-like3 receptor reveals the role of ?-catenin and Notch signaling in gubernaculum development.
pubmed:affiliation
Department of Human Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural