{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:17:01Z","timestamp":1784888221882,"version":"3.55.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,8,2]],"date-time":"2019-08-02T00:00:00Z","timestamp":1564704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH-1R15HL117238"],"award-info":[{"award-number":["NIH-1R15HL117238"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH-1R56HL138479-01"],"award-info":[{"award-number":["NIH-1R56HL138479-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dominant TBX5 mutation causes Holt-Oram syndrome (HOS), which is characterized by limb defects in humans, but the underlying mechanistic basis is unclear. We used a mouse model with Tbx5 conditional knockdown in Hh-receiving cells (marked by Gli1+) during E8 to E10.5, a previously established model to study atrial septum defects, which displayed polydactyly or hypodactyly. The results suggested that Tbx5 is required for digit identity in a subset of limb mesenchymal cells. Specifically, Tbx5 deletion in this cell population decreased cell apoptosis and increased the proliferation of handplate mesenchymal cells. Furthermore, Tbx5 was found to negatively regulate the Hh-signaling activity through transcriptional regulation of Ptch1, a known Hh-signaling repressor. Repression of Hh-signaling through Smo co-mutation in Tbx5 heterozygotes rescued the limb defects, thus placing Tbx5 upstream of Hh-signaling in limb defects. This work reveals an important missing component necessary for understanding not only limb development but also the molecular and genetic mechanisms underlying HOS.<\/jats:p>","DOI":"10.1093\/hmg\/ddz185","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T11:12:03Z","timestamp":1563966723000},"page":"1405-1416","source":"Crossref","is-referenced-by-count":5,"title":["Tbx5 inhibits hedgehog signaling in determination of digit identity"],"prefix":"10.1093","volume":"29","author":[{"given":"Huiting","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58202, USA"},{"name":"Hubei Cancer Hospital, Wuhan, Hubei 430079, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglan","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58202, 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