{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T06:46:15Z","timestamp":1760424375260},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,12,25]],"date-time":"2001-12-25T00:00:00Z","timestamp":1009238400000},"content-version":"vor","delay-in-days":493,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Growth Differ"],"published-print":{"date-parts":[[2000,8,19]]},"abstract":"<jats:p>Digit patterning is established through multiple genetic interactions. \u03b4\u2010Crystallin enhancer\/E2\u2010box factor (\u03b4EF1) is a zinc finger and homeodomain containing repressor protein, and is expressed in the posterior half of the forelimb bud and in the entire hindlimb bud during the early stage of limb development. The <jats:italic>\u03b4EF1<\/jats:italic>\u2010deficient mutant mice display various skeletal abnormalities, among which inferior ossification and abnormal patterning of autopodial bones are similar to those observed in <jats:italic>Hox<\/jats:italic> and <jats:italic>Gli<\/jats:italic> gene mutants. <jats:italic>Gli3<\/jats:italic> mutant mice, <jats:italic>extra toes<\/jats:italic> (<jats:italic>Xt<\/jats:italic>), exhibit pre\u2010axial polydactyly losing the identity of digit I. It is demonstrated here that <jats:italic>\u03b4EF1<jats:sup>null(lacZ)<\/jats:sup><\/jats:italic> homozygosity suppressed formation of the extra digit, uniquely of the hindlimb, in both <jats:italic>Gli3<jats:sup>XtJ<\/jats:sup><\/jats:italic> heterozygous and homozygous mutants, but with no restoration of digit I identity. In <jats:italic>Gli3<jats:sup>XtJ<\/jats:sup><\/jats:italic> mutants, the <jats:italic>Hoxd13<\/jats:italic> expression domain was expanded more dramatically in homozygotes. In <jats:italic>Gli3<jats:sup>XtJ<\/jats:sup>;\u03b4EF1<jats:sup>null(lacZ)<\/jats:sup><\/jats:italic> double homozygous mutants, <jats:italic>Hoxd13<\/jats:italic> expression once expanded in <jats:italic>Gli3<jats:sup>XtJ<\/jats:sup><\/jats:italic> homozygous mutant was reduced, more conspicuously in the hindlimbs, which may account for hindlimb\u2010restricted suppression of formation of the extra digit. The data suggest the possibility that the extent of <jats:italic>Hoxd13<\/jats:italic> expression along the distal margin of the limb bud is determinative in defining the digit number.<\/jats:p>","DOI":"10.1046\/j.1440-169x.2000.00523.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T14:23:54Z","timestamp":1047392634000},"page":"367-376","source":"Crossref","is-referenced-by-count":12,"title":["Suppression of polydactyly of the <i>Gli3<\/i> mutant (extra toes) by <i>\u03b4EF1<\/i> homozygous mutation"],"prefix":"10.1111","volume":"42","author":[{"given":"Hiroki","family":"Moribe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisato","family":"Kondoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujiro","family":"Higashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,12,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(97)00656-4"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1996.15.643"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.10.1767"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/342767a0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7939709"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90627-3"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(91)90048-B"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.10.6773"},{"key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1242\/dev.122.10.2997","article-title":"Hoxa\u201013 and Hoxd\u201013 play a crucial role in the patterning of the limb autopod.","volume":"122","author":"Fromental\u2010Ramain C.","year":"1996","journal-title":"Development"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.13.3543"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1242\/dev.119.2.433","article-title":"\u03b4\u2010crystallin enhancer binding protein \u03b4EF1 is a zinc finger\u2010homeodomain protein implicated in postgastrulation embryogenesis.","volume":"119","author":"Funahashi J.","year":"1993","journal-title":"Development"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.9.6153"},{"key":"e_1_2_6_14_1","unstructured":"Hogan B. Beddington R. Constantini F. Lacy E.1994. Staining embryos for cartilage and bone. InManipulating the Mouse Embryo: A Laboratory Manual(Eds B. Hogan R. Beddington F. Constantini & E. Lacy) Cold Spring Harbor Laboratory Press Cold Spring Harbor."},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(97)00065-8"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0393-241"},{"key":"e_1_2_6_17_1","first-page":"543","article-title":"Extra\u2010toes: A new mutant gene causing multiple abnormalities in the mouse.","volume":"17","author":"Johnson D. R.","year":"1967","journal-title":"J. Embryol. Exp. 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Hox genes and growth: Early and late roles in limb bud morphogenesis.Development120S 181\u2013186.","DOI":"10.1242\/dev.1994.Supplement.181"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(97)80082-2"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/371609a0"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"3999","DOI":"10.1242\/dev.124.20.3999","article-title":"Polydactyly and ectopic ZPA formation in Alx\u20104 mutant mice.","volume":"124","author":"Qu S.","year":"1997","journal-title":"Development"},{"key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1242\/dev.125.14.2711","article-title":"Mutations in mouse Aristaless\u2010like4 cause Strong\u2019s luxoid polydactyly.","volume":"125","author":"Qu S.","year":"1998","journal-title":"Development"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90626-2"},{"key":"e_1_2_6_32_1","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1242\/dev.124.7.1313","article-title":"A binding site for Gli proteins is essential for HNF\u20103\u03b2 floor plate enhancer activity in transgenics and can respond to Shh in vitro.","volume":"124","author":"Sasaki H.","year":"1997","journal-title":"Development"},{"key":"e_1_2_6_33_1","unstructured":"Saunders J. 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