{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:42:54Z","timestamp":1784090574555,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,6,3]],"date-time":"2005-06-03T00:00:00Z","timestamp":1117756800000},"content-version":"vor","delay-in-days":3686,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1995,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The roles of<jats:italic>engrailed<\/jats:italic>\u20101 (<jats:italic>En<\/jats:italic>\u20101) and<jats:italic>engrailed<\/jats:italic>\u20102 (<jats:italic>En<\/jats:italic>\u20102) have been investigated during gastrulation and neurulation in mouse embryos. Using antisense oligonucleotides and murine whole embryo culture, early somite embryos were injected with antisense phosphorothioated oligonucleotides directed against<jats:italic>En<\/jats:italic>\u20101 of<jats:italic>En<\/jats:italic>\u20102 transcripts and then grown in vitro for 48 hr. Inhibition of<jats:italic>En<\/jats:italic>\u20101 by antisense targeting during this period resulted in embryos with craniofacial abnormalities, specifically loss of mid\u2010and hindbrain tissue and hypoplasia in associated neural crest derived areas such as the face and first and second pharyngeal arches. In addition, <jats:italic>En<\/jats:italic>\u20101 appeared to be essential in early patterning of the neural tube. Embryos removed from culture as 8 hr following injection exhibited undulations in the presumptive spinal cord. Histological analysis of the affected neural tubes at 48 hr showed disrupted cytoarchitecture and in some cases, apparent dorsal\u2010ventral duplication of the neural tube and underlying notochord. Using S100 beta as a notochord marker, embryos removed from culture at 8 or 12 hr following injection exhibited loss of S100 beta expression in the notochord region subjacent to affected neural tube segments, suggesting that S100 beta, or other notochordal genes, may be downstream components of the <jats:italic>En<\/jats:italic>\u20101 regulatory cascade. Furthermore, antisense inhibition of<jats:italic>En<\/jats:italic>\u20101 induced caudal dysgenesis, suggesting disruption in primitive streak function. Antisense targeting of <jats:italic>En<\/jats:italic>\u20102 expression at early somite stages produced few alterations in development, although approximately one third of the embryos exhibited a series of lateral folds in the spinal cord at the level of the forelimb\u2010bud. Combined injections with<jats:italic>En<\/jats:italic>\u20101 and<jats:italic>En<\/jats:italic>\u20102 antisense resulted in no novel phenotypes, suggesting that the genes do not possess functional redundancy. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/tera.1420510506","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T16:08:37Z","timestamp":1118506117000},"page":"300-310","source":"Crossref","is-referenced-by-count":21,"title":["Antisense inhibition of <i>Engrailed<\/i> genes in mouse embryos reveals roles for these genes in craniofacial and neural tube development"],"prefix":"10.1002","volume":"51","author":[{"given":"Karen A.","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. 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