{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:42:57Z","timestamp":1785422577975,"version":"3.56.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,2,22]],"date-time":"2006-02-22T00:00:00Z","timestamp":1140566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The complex cardiac defects that occur in heterotaxy result from abnormal left\u2013right patterning. Mutations in the zinc finger transcription factor <jats:italic>ZIC3<\/jats:italic> cause X\u2010linked heterotaxy, HTX1. We previously have generated a targeted deletion of the murine <jats:italic>Zic3<\/jats:italic> locus and demonstrated that these knockout mice correctly model HTX1. Fifty percent of <jats:italic>Zic3<\/jats:italic> null embryos have cardiac looping anomalies at embryonic day 10.5 to 14.5, with ventral looping and sinistral looping as the predominant phenotypes. The penetrance of these phenotypes is increased in mice that are also haploinsufficient for <jats:italic>Nodal<\/jats:italic>. <jats:italic>Zic3<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup><jats:italic>; Nodal<\/jats:italic> <jats:sup>+\/\u2212<\/jats:sup> compound heterozygous mice are born in significantly reduced numbers (<jats:italic>P<\/jats:italic> = 0.0001), indicating a genetic interaction between the loci. Furthermore, an upstream <jats:italic>Nodal<\/jats:italic> enhancer is responsive to Zic3 in both <jats:italic>Xenopus<\/jats:italic> and mouse. These studies provide evidence that Zic3 interacts genetically with Nodal in left\u2013right patterning and subsequent cardiac development and delineate a critical Zic3\u2010responsive enhancer required for mediating <jats:italic>Nodal<\/jats:italic> expression at the node. Developmental Dynamics 235:1631\u20131637, 2006. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.20719","type":"journal-article","created":{"date-parts":[[2006,2,22]],"date-time":"2006-02-22T13:46:45Z","timestamp":1140616005000},"page":"1631-1637","source":"Crossref","is-referenced-by-count":49,"title":["Heart defects in X\u2010linked heterotaxy: Evidence for a genetic interaction of Zic3 with the nodal signaling pathway"],"prefix":"10.1002","volume":"235","author":[{"given":"Stephanie M.","family":"Ware","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine G.","family":"Harutyunyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Belmont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,2,22]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.12.1589"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1016202"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2004.03.003"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-305"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg732"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.22.4787"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000773200"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1084703"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008480-200106000-00002"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2004.59"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.10.1831"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200526"},{"key":"e_1_2_5_14_1","volume-title":"Normal table of Xenopus laevis","author":"Nieuwkoop PD","year":"1994"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.12.1575"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.14.3455"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.9.2293"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1084403"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80401-3"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(02)00121-5"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20192"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.19.041603.094522"},{"key":"e_1_2_5_23_1","volume-title":"Early development of Xenopus laevis. 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