{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:21:35Z","timestamp":1790612495928,"version":"4.1.0"},"reference-count":42,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,1,1]]},"abstract":"<jats:p>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+\/\u2212 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\/\u03b2-catenin and Notch pathways. We have demonstrated profound changes in the expression pattern of \u03b2-catenin, Notch1, desmin, and androgen receptor (AR), in Rxfp2\u2212\/\u2212 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 \u03b2-catenin or Notch1 in the gubernacular ligament demonstrated abnormal development. Our data indicates that \u03b2-catenin and Notch pathways are potential targets of INSL3 signaling during gubernacular development.<\/jats:p>","DOI":"10.1210\/me.2010-0330","type":"journal-article","created":{"date-parts":[[2010,12,9]],"date-time":"2010-12-09T01:56:03Z","timestamp":1291859763000},"page":"170-183","source":"Crossref","is-referenced-by-count":61,"title":["Suppression of Insulin-Like3 Receptor Reveals the Role of \u03b2-Catenin and Notch Signaling in Gubernaculum Development"],"prefix":"10.1210","volume":"25","author":[{"given":"Elena M.","family":"Kaftanovskaya","sequence":"first","affiliation":[{"name":"Department of Human and Molecular Genetics (E.M.K., Z.H., Y.T., A.B., S.K., A.T., A.I.A.), Herbert Wertheim College of Medicine, Florida International University, Miami, Florida 33199;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics (E.M.K., Z.H., Y.T., A.B., S.K., A.T., A.I.A.), Herbert Wertheim College of Medicine, Florida International University, Miami, Florida 33199;"},{"name":"Department of Obstetrics and Gynecology (S.F., A.T., A.I.A.), Baylor College of Medicine, Houston, Texas 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaohua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics (E.M.K., Z.H., Y.T., A.B., S.K., A.T., A.I.A.), Herbert Wertheim College of Medicine, Florida International University, Miami, Florida 33199;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Gynecology (Y.T.), Shandong Qianfoshan Hospital, Shandong University, Jinan, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustin M.","family":"Barbara","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics (E.M.K., Z.H., Y.T., A.B., S.K., A.T., A.I.A.), Herbert Wertheim College of Medicine, Florida International University, Miami, Florida 33199;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukhjinder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics (E.M.K., Z.H., Y.T., A.B., S.K., A.T., A.I.A.), Herbert Wertheim College of Medicine, Florida International University, Miami, Florida 33199;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics (E.M.K., Z.H., Y.T., A.B., S.K., A.T., A.I.A.), Herbert Wertheim College of Medicine, Florida International University, Miami, Florida 33199;"},{"name":"Department of Obstetrics and Gynecology (S.F., A.T., A.I.A.), Baylor College of Medicine, Houston, Texas 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan 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