{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:23:32Z","timestamp":1791325412715,"version":"4.3.1"},"reference-count":48,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[1991,12,1]],"date-time":"1991-12-01T00:00:00Z","timestamp":691545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1991,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Retinoic acid is a very potent teratogen and has also been implicated as an endogenous developmental signalling molecule in vertebrate embryos. One of the regions of the embryo reliably affected by exogenously applied RA is the hindbrain. In this paper, we describe in detail the hindbrain of Xenopus laevis embryos briefly treated with various levels of RA at gastrula stages. Such treatments lead to development of embryos with loss of anterior structures. In addition, RA has a general effect on rhombomere morphology and specific effects on the development of the anterior rhombomeres. This effect is demonstrated using neurofilament antibodies, HRP staining and in situ hybridisation using a probe for expression of the Xenopus Krox-20 gene. Anatomically it is evident that the development of the hindbrain normally anterior to the otocyst (rhombomeres 1-4) is abnormal following RA treatment. Sensory and motor axons of cranial nerves V and Vll form a single root and the peripheral paths of V and VH and IX and X are also abnormal, as is the more anterior location of the otocyst. These anatomical changes are accompanied by changes in the pattern of expression for the gene XKrox-20, which normally expresses in rhombomeres 3 and 5, but is found in a single band in the anterior hindbrain of treated embryos which standardly fail to generate the normal external segmental appearance. The results are discussed in terms of both the teratogenic and possible endogenous roles of RA during normal development of the central nervous system. We conclude that low doses of RA applied during gastrulation have specific effects on the anterior Xenopus hindbrain which appear to be evolutionarily conserved in the light of similar recent findings in zebrafish.<\/jats:p>","DOI":"10.1242\/dev.113.4.1145","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T18:26:53Z","timestamp":1619202413000},"page":"1145-1158","source":"Crossref","is-referenced-by-count":207,"title":["Retinoic acid causes abnormal development and segmental patterning of the anterior hindbrain in <i>Xenopus<\/i> embryos"],"prefix":"10.1242","volume":"113","author":[{"given":"N.","family":"Papalopulu","sequence":"first","affiliation":[{"name":"1 MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. D. W.","family":"Clarke","sequence":"additional","affiliation":[{"name":"2 Anatomy and Human Biology Group, Biomedical Sciences Division, King\u2019s College London, Strand, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Bradley","sequence":"additional","affiliation":[{"name":"1 MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"1 MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Krumlauf","sequence":"additional","affiliation":[{"name":"1 MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Holder","sequence":"additional","affiliation":[{"name":"2 Anatomy and Human Biology Group, Biomedical Sciences Division, King\u2019s College London, Strand, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1991,12,1]]},"reference":[{"key":"2023050315324722200_DEVELOP_113_4_1145C1","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1016\/0896-6273(89)90066-4","article-title":"Retinoids, homeobox genes and limb morphogenesis","volume":"2","author":"Brockes","year":"1989","journal-title":"Neuron"},{"key":"2023050315324722200_DEVELOP_113_4_1145C2","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1101\/gad.4.11.1910","article-title":"Differential activation of Xenopus homeobox genes by mesoderm-inducing growth factors and retinoic acid","volume":"4","author":"Cho","year":"1990","journal-title":"Genes Dev"},{"key":"2023050315324722200_DEVELOP_113_4_1145C3","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0092-8674(91)90407-P","article-title":"Overexpression of a homeodomain protein confers axis-forming activity to uncommitted Xenopus embryonic cells","volume":"65","author":"Cho","year":"1991","journal-title":"Cell"},{"key":"2023050315324722200_DEVELOP_113_4_1145C4","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1242\/dev.105.1.61","article-title":"A wholemount immmunocytochemical analysis of the expression of the intermediate filament protein vimentin in Xenopus","volume":"105","author":"Dent","year":"1989","journal-title":"Development"},{"key":"2023050315324722200_DEVELOP_113_4_1145C5","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1002\/j.1460-2075.1989.tb03534.x","article-title":"The murine Hox gene network\u2019 its structural and functional organisation resembles that of Drosophila homeotic genes","volume":"8","author":"Duboule","year":"1989","journal-title":"EMBO J"},{"key":"2023050315324722200_DEVELOP_113_4_1145C6","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1038\/340140a0","article-title":"Retinoic acid causes an anteroposterior transformation in the developing central nervous system","volume":"340","author":"Durston","year":"1989","journal-title":"Nature"},{"key":"2023050315324722200_DEVELOP_113_4_1145C7","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/344431a0","article-title":"Segmentation in the chick embryo hindbrain is defined by cell lineage restrictions","volume":"344","author":"Fraser","year":"1990","journal-title":"Nature"},{"key":"2023050315324722200_DEVELOP_113_4_1145C8","doi-asserted-by":"publisher","first-page":"351","DOI":"10.3109\/10408447909043651","article-title":"Hypervitaminosis A-induced teratogenesis","volume":"6","author":"Geelan","year":"1979","journal-title":"CRC Crit. 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