{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:32:47Z","timestamp":1791178367244,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,2,6]],"date-time":"2005-02-06T00:00:00Z","timestamp":1107648000000},"content-version":"vor","delay-in-days":4419,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev. Genet."],"published-print":{"date-parts":[[1993,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Wnt\u20101<\/jats:italic> and <jats:italic>Wnt\u20103a<\/jats:italic> proto\u2010on\u2010cogenes have been implicated in the development of midbrain and hindbrain structures. Evidence for such a role has been derived from in situ hybridization studies showing <jats:italic>Wnt\u20101<\/jats:italic> and <jats:italic>\u20103a<\/jats:italic> expression in developing cranial and spinal cord regions and from studies of mutant mice whose <jats:italic>Wnt\u20101<\/jats:italic> genes have undergone targeted disruption by homologous recombination. <jats:italic>Wnt\u20101<\/jats:italic> null mutants exhibit cranial defects but no spinal cord abnormalities, despite expression of the gene in these regions. The absence of spinal cord abnormalities is thought to be due to a functional compensation of the <jats:italic>Wnt\u20101<\/jats:italic> deficiency by related genes, a problem that has complicated the analysis of null mutants of other developmental genes as well. Herein, we describe the attenuation of <jats:italic>Wnt\u20101<\/jats:italic> expression using antisense oligonucleotide inhibition in mouse embryos grown in culture. We induce similar mid\u2010 and hindbrain abnormalities as those seen in the <jats:italic>Wnt\u20101<\/jats:italic> null mutant mice. Attentuation of <jats:italic>Wnt\u20101<\/jats:italic> expression was also associated with cardiomegaly resulting in hemostasis. These findings are consistent with the possibility that a subset of <jats:italic>Wnt\u20101<\/jats:italic> expressing cells include neural crest cells known to contribute to septation of the truncus arteriosus and to formation of the visceral arches. Antisense knockout of <jats:italic>Wnt\u20103a<\/jats:italic>, a gene structurely related to <jats:italic>Wnt\u20101<\/jats:italic>, targeted the forebrain and midbrain region, which were hy\u2010poplastic and failed to expand, and the spinal cord, which exhibited lateral outpocketings at the level of the forelimb buds. Dual antisense knockouts of <jats:italic>Wnt\u20101<\/jats:italic> and <jats:italic>Wnt\u20103a<\/jats:italic> targeted all brain regions leading to incomplete closure of the cranial neural folds, and an increase in the number and severity of outpocketings along the spinal cord, suggesting that these genes complement one another to produce normal patterning of the spinal cord. The short time required to assess the mutant phenotype (2 days) and the need for limited sequence information of the target gene (20\u201025 nu\u2010cleotides) make this antisense oligonucleotide\/ whole embryo culture system ideal for testing the importance of specific genes and their interactions in murine embryonic development. \u00a9 1993 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvg.1020140611","type":"journal-article","created":{"date-parts":[[2005,5,25]],"date-time":"2005-05-25T22:39:03Z","timestamp":1117060743000},"page":"500-520","source":"Crossref","is-referenced-by-count":72,"title":["Antisense attenuation of <i>Wnt\u20101<\/i> and <i>Wnt\u20103a<\/i> expression in whole embryo culture reveals roles for these genes in craniofacial, spinal cord, and cardiac morphogenesis"],"prefix":"10.1002","volume":"14","author":[{"given":"Karen","family":"Augustine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edison T.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. W.","family":"Sadler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,2,6]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001800403"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910540409"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420330112"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2.12b.1736"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.111.2.287"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1242\/dev.105.1.61","article-title":"A whole\u2010mount im\u2010munocytochemical analysis of the expression of the intermediate filament protein vimentin in Xenopus","volume":"105","author":"Dent JA","year":"1989","journal-title":"Development"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/356215a0"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1279811"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1402450306"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198703000-00001"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6844926"},{"key":"e_1_2_1_14_1","first-page":"125","article-title":"Mesenchymal derivatives of the neural crest: Analysis of chimeric quail and chick embryos","volume":"34","author":"LeLievre CS","year":"1975","journal-title":"J Em\u2010bryol Exp Morphol"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb03367.x"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90385-R"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90222-X"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.5.691"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-185X.1978.tb00993.x"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.75.1.255"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.3.381"},{"key":"e_1_2_1_22_1","first-page":"17","article-title":"Culture of early somite mouse embryos during organogenesis","volume":"49","author":"Sadler TW","year":"1979","journal-title":"J Embryol Exp Morphol"},{"key":"e_1_2_1_23_1","first-page":"861","article-title":"Embryonic lethality resulting from disruption of both N\u2010myc alleles in mouse zygotes","volume":"3","author":"Sawai S","year":"1991","journal-title":"New Biol"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.117.4.1445"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90499-O"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.59.5.545"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/346847a0"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90369-A"},{"key":"e_1_2_1_29_1","first-page":"211","article-title":"Isotretin\u2010oin embryopathy and the cranial neural crest: An in vivo and in vitro study","volume":"6","author":"Webster WS","year":"1986","journal-title":"J Craniofacial Genet"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90664-7"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.22.10023"}],"container-title":["Developmental Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdvg.1020140611","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvg.1020140611","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T06:48:30Z","timestamp":1698302910000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dvg.1020140611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,1]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1993,1]]}},"alternative-id":["10.1002\/dvg.1020140611"],"URL":"https:\/\/doi.org\/10.1002\/dvg.1020140611","archive":["Portico"],"relation":{},"ISSN":["0192-253X","1520-6408"],"issn-type":[{"value":"0192-253X","type":"print"},{"value":"1520-6408","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,1]]}}}