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| Status |
Public on Nov 10, 2010 |
| Title |
Suppression of insulin like3 receptor reveals the role of β-catenin and Notch signaling in gubernaculum development |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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 INSL3, insulin like3 hormone, 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/β-catenin and Notch pathways. We have demonstrated profound changes in the expression pattern of β-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 β-catenin or Notch1 in the gubernacular ligament demonstrated abnormal development. Our data indicates that β-catenin and Notch pathways are potential targets of INSL3 signaling during gubernacular development.
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| Overall design |
Total RNA obtained from the cremasteric sac of cryptorchid Tg(shRxfp1) males compared to the wild-type control cremasteric sac.
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| Contributor(s) |
Agoulnik A |
| Citation(s) |
21147849 |
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| Submission date |
Nov 09, 2010 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Alexander I Agoulnik |
| E-mail(s) |
aagoulni@fiu.edu
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| Organization name |
Florida International University
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| Department |
Herbert Wertheim College of Medicine
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| Street address |
11200 SW 8th Street, HLSI 419B
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| City |
Miami |
| State/province |
FL |
| ZIP/Postal code |
33199 |
| Country |
USA |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA134459 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE25222_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE25222_non-normalized.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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