{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:27:58Z","timestamp":1761920878737,"version":"3.37.1"},"reference-count":41,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[1998,2,1]],"date-time":"1998-02-01T00:00:00Z","timestamp":886291200000},"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":[[1998,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The mouse mutant Doublefoot (Dbf) shows preaxial polydactyly of all four limbs. We have analysed limb development in this mutant with respect to morphogenesis, gene expression patterns and ectopic polarising activity. The results reveal a gain-of-function mutation at a locus that mediates pattern formation in the developing limb. Shh expression is identical with that of wild-type embryos, i.e. there is no ectopic expression. However, mesenchyme from the anterior aspects of Dbf\/+ mutant limb buds, when transplanted to the anterior side of chick wing buds, induces duplication of the distal skeletal elements. Middistal mesenchymal transplants from early, but not later, Dbf\/+ limb buds are also able to induce duplication. This demonstration of polarising activity in the absence of Shh expression identifies the gene at the Dbf locus as a new genetic component of the Shh signalling pathway, which (at least in its mutated form) is able to activate signal transduction independently of Shh. The mutant gene product is sufficient to fulfil the signalling properties of Shh including upregulation of the direct Shh target genes Ptc and Gli, and induction of the downstream target genes Bmp2, Fgf4 and Hoxd13. The expression domains of all these genes extend from their normal posterior domains into the anterior part of the limb bud without being focused on a discrete ectopic site. These observations dissociate polarising activity from Shh gene expression in the Dbf\/+ limb bud. We suggest that the product of the normal Dbf gene is a key active constituent of the polarising region, possibly acting in the extracellular compartment.<\/jats:p>","DOI":"10.1242\/dev.125.3.351","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:30:46Z","timestamp":1619407846000},"page":"351-357","source":"Crossref","is-referenced-by-count":21,"title":["<i>Sonic hedgehog<\/i> is not required for polarising activity in the <i>Doublefoot<\/i> mutant mouse limb bud"],"prefix":"10.1242","volume":"125","author":[{"given":"Christopher","family":"Hayes","sequence":"first","affiliation":[{"name":"University of Oxford 1 Department of Human Anatomy , , South Parks Road, Oxford, OX1 3QX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Brown","sequence":"additional","affiliation":[{"name":"University of Oxford 1 Department of Human Anatomy , , South Parks Road, Oxford, OX1 3QX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary F.","family":"Lyon","sequence":"additional","affiliation":[{"name":"2 MRC Mammalian Genetics Unit, Harwell, Didcot, Oxfordshire, OX11 0RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian M.","family":"Morriss-Kay","sequence":"additional","affiliation":[{"name":"University of Oxford 1 Department of Human Anatomy , , South Parks Road, Oxford, OX1 3QX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1998,2,1]]},"reference":[{"key":"2025021410171033100_DEVELOP_125_3_351C1","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1101\/gad.10.16.2003","article-title":"Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the Cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins","volume":"10","author":"Alexandre","year":"1996","journal-title":"Genes Dev"},{"key":"2025021410171033100_DEVELOP_125_3_351C2","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1242\/dev.121.7.1971","article-title":"Polydactylous limbs in Strongs luxoid mice results from ectopic polarizing activity","volume":"121","author":"Chan","year":"1995","journal-title":"Development"},{"key":"2025021410171033100_DEVELOP_125_3_351C3","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/S0092-8674(00)81374-4","article-title":"Dual roles for Patched in sequestering and transducing hedgehog","volume":"87","author":"Chen","year":"1996","journal-title":"Cell"},{"key":"2025021410171033100_DEVELOP_125_3_351C4","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1242\/dev.122.6.1821","article-title":"Activation of Fgf-4 and HoxD gene expression by BMP-2 expressing cells in the developing chick limb","volume":"122","author":"Duprez","year":"1996","journal-title":"Development"},{"key":"2025021410171033100_DEVELOP_125_3_351C5","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1242\/dev.120.1.209","article-title":"Bone morphogenetic proteins and a signalling pathway that controls patterning in the developing chick limb","volume":"120","author":"Francis","year":"1994","journal-title":"Development"},{"key":"2025021410171033100_DEVELOP_125_3_351C6","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/aja.1002030207","article-title":"Expression of genes encoding bone morphogenetic proteins and Sonic hedgehog in Talpid (ta3) limb buds: their relationships in the signalling cascade involved in limb patterning","volume":"203","author":"Francis-West","year":"1995","journal-title":"Dev. 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