{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T02:34:43Z","timestamp":1781231683954,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["1R15 HD095368"],"award-info":[{"award-number":["1R15 HD095368"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The penile tubular urethra forms by canalization of the urethral plate without forming an obvious urethral groove in mice, while the urethral epithelium forms a fully open urethral groove before urethra closure through the distal-opening-proximal-closing process in humans and guinea pigs. Our knowledge of the mechanism of penile development is mainly based on studies in mice. To reveal how the fully opened urethral groove forms in humans and guinea pigs, we compared the expression patterns and levels of key developmental genes using in situ hybridization and quantitative PCR during glans and preputial development between guinea pigs and mice. Our results revealed that, compared with mouse preputial development, which started before sexual differentiation, preputial development in guinea pigs was delayed and initiated at the same time that sexual differentiation began. Fgf10 was mainly expressed in the urethral epithelium in developing genital tubercle (GT) of guinea pigs. The relative expression of Shh, Fgf8, Fgf10, Fgfr2, and Hoxd13 was reduced more than 4-fold in the GT of guinea pigs compared to that of mice. Hedgehog and Fgf inhibitors induced urethral groove formation and restrained preputial development in cultured mouse GT, while Shh and Fgf10 proteins induced preputial development in cultured guinea pig GT. Our discovery suggests that the differential expression of Shh and Fgf10\/Fgfr2 may be the main reason a fully opened urethral groove forms in guinea pigs, and it may be similar in humans as well.<\/jats:p>","DOI":"10.3390\/cells14050348","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T04:28:18Z","timestamp":1740716898000},"page":"348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differences in Formation of Prepuce and Urethral Groove During Penile Development Between Guinea Pigs and Mice Are Controlled by Differential Expression of Shh, Fgf10 and Fgfr2"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4836-3041","authenticated-orcid":false,"given":"Shanshan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-2976","authenticated-orcid":false,"given":"Zhengui","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.juro.2014.09.108","article-title":"Canalization of the urethral plate precedes fusion of the urethral folds during male penile urethral development: The double zipper hypothesis","volume":"193","author":"Li","year":"2015","journal-title":"J. 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