{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:48:48Z","timestamp":1791406128646,"version":"4.3.3"},"reference-count":48,"publisher":"Cold Spring Harbor Laboratory","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[2002,5,1]]},"abstract":"<jats:p>\n                    <jats:italic>Dlx<\/jats:italic>\n                    homeobox genes are mammalian homologs of the\n                    <jats:italic>Drosophila Distal-less<\/jats:italic>\n                    (\n                    <jats:italic>Dll<\/jats:italic>\n                    ) gene. The\n                    <jats:italic>Dlx<\/jats:italic>\n                    \/\n                    <jats:italic>Dll<\/jats:italic>\n                    gene family is of ancient origin and appears to play a role in appendage development in essentially all species in which it has been identified. In\n                    <jats:italic>Drosophila<\/jats:italic>\n                    ,\n                    <jats:italic>Dll<\/jats:italic>\n                    is expressed in the distal portion of the developing appendages and is critical for the development of distal structures. In addition, human\n                    <jats:italic>Dlx5<\/jats:italic>\n                    and\n                    <jats:italic>Dlx6<\/jats:italic>\n                    homeobox genes have been identified as possible candidate genes for the autosomal dominant form of the split-hand\/split-foot malformation (SHFM), a heterogeneous limb disorder characterized by missing central digits and claw-like distal extremities. Targeted inactivation of\n                    <jats:italic>Dlx5<\/jats:italic>\n                    and\n                    <jats:italic>Dlx6<\/jats:italic>\n                    genes in mice results in severe craniofacial, axial, and appendicular skeletal abnormalities, leading to perinatal lethality. For the first time,\n                    <jats:italic>Dlx<\/jats:italic>\n                    \/\n                    <jats:italic>Dll<\/jats:italic>\n                    gene products are shown to be critical regulators of mammalian limb development, as combined loss-of-function mutations phenocopy SHFM. Furthermore, spatiotemporal-specific transgenic overexpression of\n                    <jats:italic>Dlx5<\/jats:italic>\n                    , in the apical ectodermal ridge of\n                    <jats:italic>Dlx5\/6<\/jats:italic>\n                    null mice can fully rescue\n                    <jats:italic>Dlx<\/jats:italic>\n                    \/\n                    <jats:italic>Dll<\/jats:italic>\n                    function in limb outgrowth.\n                  <\/jats:p>","DOI":"10.1101\/gad.988402","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T20:00:38Z","timestamp":1027713638000},"page":"1089-1101","source":"Crossref","is-referenced-by-count":386,"title":["The\n                    <i>Dlx5<\/i>\n                    and\n                    <i>Dlx6<\/i>\n                    homeobox genes are essential for craniofacial, axial, and appendicular skeletal development"],"prefix":"10.1101","volume":"16","author":[{"given":"Raymond 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