{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:30:31Z","timestamp":1791203431201,"version":"4.2.0"},"reference-count":72,"publisher":"The Company of Biologists","issue":"2","license":[{"start":{"date-parts":[[1993,10,1]],"date-time":"1993-10-01T00:00:00Z","timestamp":749433600000},"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":[[1993,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>This study provides a detailed description of the anatomical defects in the Hoxa-1\u2212\/\u2212mutant mice previously generated in our laboratory (T. Lufkin, A. Dierich, M. LeMeur, M. Mark and P. Chambon, 1991; Cell 66, 1105-1119). Three-dimensional reconstructions of the Hoxa-1\u2212\/\u2212 rhombencephalon reveals that it bears only five rhombomeric structures (ie. morphological segments) instead of the normal seven. The first three of these rhombomeres appear normal as judged from the distribution pattern of CRABPI transcripts in the neurectoderm and from the histological analysis of the cranial nerve components derived from these structures. In contrast, the neural-crest-cell-free region normally located opposite rhombomere 5 is lacking in Hoxa-1\u2212\/\u2212 embryos, and motor neurons of the facial and abducens nerves, which normally differentiate within rhombomeres 4, 5 and 6, are missing in Hoxa-1\u2212\/\u2212 fetuses. These morphological data, combined with the determination of the molecular positional identities of the rhombomeres 4 and 5 (P. Doll\u00e9, T. Lufkin, R. Krumlauf, M. Mark, D. Duboule and P. Chambon, 1993; Proc. Natl. Acad. Sci. USA, in press), suggest that rhombomere 4 is markedly reduced, whereas rhombomere 5 is almost absent. Thus, the remnants of rhombomeres 4 and 5 appear to be fused caudally with rhombomere 6 to form a single fourth rhombomeric structure. Moreover, the migration of neural crest cells contributing to the glossopharyngeal and vagus nerves occurs in a more rostral position, resulting in abnormalities of these cranial nerves, which were visualized by whole-mount anti-neurofilament immunostaining. The mutual relationship along the rostrocaudal axis between the otic pit and the neuroepithelial site of int-2 protein secretion (a putative otogenic cue) is not significantly changed in Hoxa-1\u2212\/\u2212 embryos. However, the abnormal relationship between the rhombencephalon and the epithelial inner ear may account for the aplasia and faulty differentiation of the membranous labyrinth, the disruption of the cartilaginous otic capsule and the disorganisation of some middle ear structures. This phenotype is compared with that of the Hoxa-1\u2212\/\u2212 mutants generated by O. Chisaka, T. S. Musci and M. R. Capecchi, 1992 (Nature 335, 516-520) and with that of the mice homozygous for the kreisler mutation.<\/jats:p>","DOI":"10.1242\/dev.119.2.319","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T01:16:40Z","timestamp":1619399800000},"page":"319-338","source":"Crossref","is-referenced-by-count":352,"title":["Two rhombomeres are altered in <i>Hoxa-1<\/i> mutant mice"],"prefix":"10.1242","volume":"119","author":[{"given":"Manuel","family":"Mark","sequence":"first","affiliation":[{"name":"1 Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l\u2019INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 11, rue Humann, 67085 Strasbourg-C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lufkin","sequence":"additional","affiliation":[{"name":"1 Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l\u2019INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 11, rue Humann, 67085 Strasbourg-C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Vonesch","sequence":"additional","affiliation":[{"name":"1 Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l\u2019INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 11, rue Humann, 67085 Strasbourg-C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Ruberte","sequence":"additional","affiliation":[{"name":"1 Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l\u2019INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 11, rue Humann, 67085 Strasbourg-C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Olivo","sequence":"additional","affiliation":[{"name":"2 European Molecular Biology Laboratory, Physical Instrumentation Programme, Meyerhofstrasse 1, W-69012 Heidelberg, FRG"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Doll\u00e9","sequence":"additional","affiliation":[{"name":"1 Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l\u2019INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 11, rue Humann, 67085 Strasbourg-C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gorry","sequence":"additional","affiliation":[{"name":"1 Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l\u2019INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 11, rue Humann, 67085 Strasbourg-C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Lumsden","sequence":"additional","affiliation":[{"name":"3 UMDS, Division of Anatomy and Cell Biology, Guy\u2019s Hospital, London Bridge, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chambon","sequence":"additional","affiliation":[{"name":"1 Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l\u2019INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 11, rue Humann, 67085 Strasbourg-C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1993,10,1]]},"reference":[{"key":"2024121723091918800_DEVELOP_119_2_319C1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/0092-8674(89)90909-4","article-title":"Hox and HOM: Homologous gene clusters in insects and vertebrates","volume":"57","author":"Akam","year":"1989","journal-title":"Cell"},{"key":"2024121723091918800_DEVELOP_119_2_319C2","volume-title":"An Introduction to Embryology","author":"Balinsky","year":"1970"},{"key":"2024121723091918800_DEVELOP_119_2_319C3","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/350473a0","article-title":"Regionally restricted developmental defects resulting from targeted disruption of the mouse homebox gene 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