{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:44:59Z","timestamp":1791121499957,"version":"4.1.0"},"reference-count":65,"publisher":"The Company of Biologists","issue":"14","license":[{"start":{"date-parts":[[1998,7,15]],"date-time":"1998-07-15T00:00:00Z","timestamp":900460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Mutations that affect vertebrate limb development provide insight into pattern formation, evolutionary biology and human birth defects. Patterning of the limb axes depends on several interacting signaling centers; one of these, the zone of polarizing activity (ZPA), comprises a group of mesenchymal cells along the posterior aspect of the limb bud that express sonic hedgehog (Shh) and plays a key role in patterning the anterior-posterior (AP) axis. The mechanisms by which the ZPA and Shh expression are confined to the posterior aspect of the limb bud mesenchyme are not well understood. The polydactylous mouse mutant Strong\u2019s luxoid (lst) exhibits an ectopic anterior ZPA and expression of Shh that results in the formation of extra anterior digits. Here we describe a new chlorambucil-induced deletion allele, lstAlb, that uncovers the lst locus. Integration of the lst genetic and physical maps suggested the mouse Aristaless-like4 (Alx4) gene, which encodes a paired-type homeodomain protein that plays a role in limb patterning, as a strong molecular candidate for the Strong\u2019s luxoid gene. In genetic crosses, the three lst mutant alleles fail to complement an Alx4 gene-targeted allele. Molecular and biochemical characterization of the three lst alleles reveal mutations of the Alx4 gene that result in loss of function. Alx4 haploinsufficiency and the importance of strain-specific modifiers leading to polydactyly are indicative of a critical threshold requirement for Alx4 in a genetic program operating to restrict polarizing activity and Shh expression in the anterior mesenchyme of the limb bud, and suggest that mutations in Alx4 may also underlie human polydactyly.<\/jats:p>","DOI":"10.1242\/dev.125.14.2711","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:18:12Z","timestamp":1619407092000},"page":"2711-2721","source":"Crossref","is-referenced-by-count":114,"title":["Mutations in mouse <i>Aristaless-like4<\/i> cause <i>Strong\u2019s luxoid<\/i> polydactyly"],"prefix":"10.1242","volume":"125","author":[{"given":"Shimian","family":"Qu","sequence":"first","affiliation":[{"name":"1 Departments of Biochemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Craig","family":"Tucker","sequence":"additional","affiliation":[{"name":"1 Departments of Biochemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Ehrlich","sequence":"additional","affiliation":[{"name":"Princeton University 3 Department of Molecular Biology, Washington Road , , Princeton, NJ 08544, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Levorse","sequence":"additional","affiliation":[{"name":"Princeton University 3 Department of Molecular Biology, Washington Road , , Princeton, NJ 08544, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine A.","family":"Flaherty","sequence":"additional","affiliation":[{"name":"4 Molecular Genetics Program, Wadsworth Center, Albany, NY 12201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Wisdom","sequence":"additional","affiliation":[{"name":"1 Departments of Biochemistry"},{"name":"Vanderbilt University School of Medicine 2 Medicine , , Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Vogt","sequence":"additional","affiliation":[{"name":"Princeton University 3 Department of Molecular Biology, Washington Road , , Princeton, NJ 08544, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1998,7,15]]},"reference":[{"key":"2025021501271355100_DEVELOP_125_14_2711C1","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1093\/nar\/19.9.2499","article-title":"A rapid micropreparation technique for the extraction of DNA-binding proteins from limiting numbers of mammalian cells","volume":"19","author":"Andrews","year":"1991","journal-title":"Nucleic Acid Res"},{"key":"2025021501271355100_DEVELOP_125_14_2711C2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1101\/gad.11.1.1","article-title":"Mouse models of human disease. 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