{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:51:55Z","timestamp":1790016715405,"version":"4.0.1"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"4","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["R01HD039963"],"award-info":[{"award-number":["R01HD039963"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["R01HD094698"],"award-info":[{"award-number":["R01HD094698"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007172","name":"Cincinnati Children\u2019s Hospital Medical Center","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100007172","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,1,27]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Platelet-derived growth factor receptor alpha<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Pdgfra<\/jats:italic>\n                    ) plays a crucial role in mesenchymal cell differentiation, but the molecular signaling involved in this process remains unclear, particularly within the fetal testis. Here, we use XY\n                    <jats:italic toggle=\"yes\">Pdgfra<\/jats:italic>\n                    -null gonads to investigate the molecular mechanisms underlying testicular organogenesis, focusing on the formation of testicular architecture and the differentiation of fetal Leydig cells (FLCs), the steroidogenic lineage arising from mesenchymal precursors within the testicular interstitial compartment. The extracellular signal-regulated kinase (ERK) pathway, a well-known mitogen-activated signaling pathway, was significantly inhibited in XY\n                    <jats:italic toggle=\"yes\">Pdgfra<\/jats:italic>\n                    -null gonads, suggesting that ERK signaling is activated downstream of PDGFRA. Using ex vivo whole-organ culture, small interfering RNA cell culture methods, transwell assays, and a genetic mouse model to disrupt ERK signaling in gonadal cells, we found that the ERK pathway promotes testis cord formation via\n                    <jats:italic toggle=\"yes\">early growth response 1<\/jats:italic>\n                    -mediated cell migration and regulates the expression of steroidogenic enzymes in FLCs via activating the transcription factor cAMP responsive element binding protein 1. These findings highlight the significance of the PDGFRA signaling network in fetal testis organogenesis, thus providing insights into mesenchymal cell differentiation and the etiology of congenital disorders related to gonadal development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2515138123","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T18:45:37Z","timestamp":1769021137000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Platelet-derived growth factor receptor alpha regulates fetal testis differentiation via an ERK\u2013CREB axis"],"prefix":"10.1073","volume":"123","author":[{"given":"Shu-Yun","family":"Li","sequence":"first","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center","place":["Cincinnati"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2460-0313","authenticated-orcid":false,"given":"Satoko","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center","place":["Cincinnati"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Whiteside","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center","place":["Cincinnati"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Gu","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center","place":["Cincinnati"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonah","family":"Cool","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Duke University Medical Center","place":["Durham"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6587-0969","authenticated-orcid":false,"given":"Blanche","family":"Capel","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Duke University Medical Center","place":["Durham"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4133-7040","authenticated-orcid":false,"given":"Tony","family":"DeFalco","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center","place":["Cincinnati"]},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine","place":["Cincinnati"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087281"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00721"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.16.1875"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.16.1888"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.16.3457"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.12.2611"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.3.457"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.5.1019"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1052503"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-194654"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.642547"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00059.2016"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2009.02.002"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.8.8147"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.177139"},{"key":"e_1_3_4_16_2","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo Y. J.","year":"2020","unstructured":"Y. J. Guo , ERK\/MAPK signalling pathway and tumorigenesis. Exp. Ther. Med. 19, 1997\u20132007 (2020).","journal-title":"Exp. Ther. Med."},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2011-0059"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0030"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.006254"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.115.137117"},{"key":"e_1_3_4_21_2","first-page":"570","article-title":"The fate of leydig cells in men with spermatogenic failure","volume":"12","author":"Adamczewska D.","year":"2022","unstructured":"D. Adamczewska, J. Slowikowska-Hilczer, R. Walczak-Jedrzejowska, The fate of leydig cells in men with spermatogenic failure. 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Li, S. Zhang, X. Soto, S. Woolner, E. Amaya, ERK and phosphoinositide 3-kinase temporally coordinate different modes of actin-based motility during embryonic wound healing. J. Cell Sci. 126, 5005\u20135017 (2013).","journal-title":"J. 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Li CREB and H3K4 CUT&RUN seq of mouse fetal testis. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE296129. 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