{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:49:03Z","timestamp":1790844543640,"version":"4.1.0"},"reference-count":107,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2016,4,5]],"date-time":"2016-04-05T00:00:00Z","timestamp":1459814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,4,5]],"date-time":"2016-04-05T00:00:00Z","timestamp":1459814400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,4,5]],"date-time":"2016-04-05T00:00:00Z","timestamp":1459814400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Crucial roles for T-box3 in development are evident by severe limb malformations and other birth defects caused by T-box3 mutations in humans. Mechanisms whereby T-box3 regulates limb development are poorly understood. We discovered requirements for T-box at multiple stages of mouse limb development and distinct molecular functions in different tissue compartments. Early loss of T-box3 disrupts limb initiation, causing limb defects that phenocopy Sonic Hedgehog (Shh) mutants. Later ablation of T-box3 in posterior limb mesenchyme causes digit loss. In contrast, loss of anterior T-box3 results in preaxial polydactyly, as seen with dysfunction of primary cilia or Gli3-repressor. Remarkably, T-box3 is present in primary cilia where it colocalizes with Gli3. T-box3 interacts with Kif7 and is required for normal stoichiometry and function of a Kif7\/Sufu complex that regulates Gli3 stability and processing. Thus, T-box3 controls digit number upstream of Shh-dependent (posterior mesenchyme) and Shh-independent, cilium-based (anterior mesenchyme) Hedgehog pathway function.<\/jats:p>","DOI":"10.7554\/elife.07897","type":"journal-article","created":{"date-parts":[[2016,4,4]],"date-time":"2016-04-04T05:59:20Z","timestamp":1459749560000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.07897","source":"Crossref","is-referenced-by-count":37,"title":["T-box3 is a ciliary protein and regulates stability of the Gli3 transcription factor to control digit number"],"prefix":"10.7554","volume":"5","author":[{"given":"Uchenna","family":"Emechebe","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Kumar P","sequence":"additional","affiliation":[{"name":"Weis Center for Research, Geisinger Clinic, Danville, United 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