{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T22:27:13Z","timestamp":1780352833874,"version":"3.54.1"},"reference-count":65,"publisher":"Cold Spring Harbor Laboratory","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1995,10,15]]},"abstract":"<jats:p>Genetic analysis of the development and evolution of the vertebrate head is at a primitive stage. Many homeo box genes, including the Distal-less family, are potential regulators of head development. To determine the function of Dlx-2, we generated a null mutation in mice using gene targeting. In homozygous mutants, differentiation within the forebrain is abnormal and the fate of a subset of cranial neural crest cells is respecified. The latter causes abnormal morphogenesis of the skeletal elements derived from the proximal parts of the first and second branchial arches. We hypothesize that the affected skull bones from the first arch have undergone a transformation into structures similar to those found in reptiles. These results show that Dlx-2 controls development of the branchial arches and the forebrain and suggests its role in craniofacial evolution.<\/jats:p>","DOI":"10.1101\/gad.9.20.2523","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T21:15:46Z","timestamp":1181078146000},"page":"2523-2538","source":"Crossref","is-referenced-by-count":325,"title":["Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain."],"prefix":"10.1101","volume":"9","author":[{"given":"M","family":"Qiu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Bulfone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J J","family":"Meneses","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Shimamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J L","family":"Rubenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1995,10,15]]},"reference":[{"key":"2021111418255384000_9.20.2523.1","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1523\/JNEUROSCI.14-06-03475.1994","article-title":"Combinational expression of three zebrafish genes related to Distal-Less: Part of a homeo box gene code for the head.","volume":"14","year":"1994","journal-title":"J. Neurosci."},{"key":"2021111418255384000_9.20.2523.2","unstructured":"Barghusen, H.R. and J.A. Hopson. 1979. The endoskeleton: The comparative anatomy of the skull and the visceral skeleton. In Hyman's comparative certebrate anatomy, 3rd ed., pp. 265\u2013326. The University of Chicago Press, Chicago, Il."},{"key":"2021111418255384000_9.20.2523.3","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1242\/dev.112.1.301","article-title":"Common precursors for neural and mesectodermal derivatives in the cephalic neural crest.","volume":"112","year":"1991","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.4","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(92)90047-K"},{"key":"2021111418255384000_9.20.2523.5","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(89)90244-4"},{"key":"2021111418255384000_9.20.2523.6","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(93)90071-5"},{"key":"2021111418255384000_9.20.2523.7","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1523\/JNEUROSCI.13-07-03155.1993","article-title":"Spatially restricted expression of Dlx-1, Dlx-2(Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries.","volume":"13","year":"1993","journal-title":"J. Neurosci."},{"key":"2021111418255384000_9.20.2523.8","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1242\/dev.118.4.1063","article-title":"Loss of Hox-a1 (Hox 1.6) function results in the reorganization of the murine hindrbrain.","volume":"118","year":"1993","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.9","doi-asserted-by":"publisher","DOI":"10.1038\/350473a0"},{"key":"2021111418255384000_9.20.2523.10","doi-asserted-by":"publisher","DOI":"10.1038\/355516a0"},{"key":"2021111418255384000_9.20.2523.11","doi-asserted-by":"publisher","DOI":"10.1038\/338432a0"},{"key":"2021111418255384000_9.20.2523.12","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1242\/dev.117.2.409","article-title":"The triple origin of skull in higher vertebrates: A study in quail-chick chimeras.","volume":"117","year":"1993","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.13","first-page":"1089","article-title":"MHox: A mesodermally restricted homeodomain protein that binds an essential site in a muscle creatine kinase enhancer.","volume":"115","year":"1992","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.14","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2.12b.1736"},{"key":"2021111418255384000_9.20.2523.15","unstructured":"de Beer, G.R. 1985. The Development of the vertebrate skull. The University of Chicago Press, Chicago, Il."},{"key":"2021111418255384000_9.20.2523.16","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(93)90042-V"},{"key":"2021111418255384000_9.20.2523.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.16.7666"},{"key":"2021111418255384000_9.20.2523.18","unstructured":"Farbman, A.I. 1991. Developmental neurobiology of the olfactory system. In Smell and taste in health and disease (ed. T.V. Getchell), pp. 19\u201333. Raven Press, New York."},{"key":"2021111418255384000_9.20.2523.19","unstructured":"Feduccio, A. and E. McCrady. 1991. The skeleton. In Torrey's morphogenesis of the vertebrates, 5th ed., pp. 201\u2013251. Wiley, New York."},{"key":"2021111418255384000_9.20.2523.20","first-page":"337","article-title":"The cranial morphology of Thrinaxodon liorhinus seeley.","volume":"65","year":"1974","journal-title":"Ann. S. Afr. Mus."},{"key":"2021111418255384000_9.20.2523.21","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1242\/dev.117.2.769","article-title":"Expression of the mouse goosecoid gene during mid-embryogenesis may mark mesenchymal lineages in the developing head, limbs, and body wall.","volume":"117","year":"1993","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.22","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90619-2"},{"key":"2021111418255384000_9.20.2523.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.2506639"},{"key":"2021111418255384000_9.20.2523.24","unstructured":"Joyner, A.L. 1994. Gene targeting. Oxford University Press, New York."},{"key":"2021111418255384000_9.20.2523.25","doi-asserted-by":"publisher","DOI":"10.1126\/science.1672471"},{"key":"2021111418255384000_9.20.2523.26","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(93)90203-T"},{"key":"2021111418255384000_9.20.2523.27","unstructured":"Langille, R.M. and B.K. Hall. 1993. Pattern formation and the neural crest. In The skull, Vol. 1 (ed. J. Hanken and B.K. Hall), pp. \u2013The University of Chicago Press, Chicago, Il."},{"key":"2021111418255384000_9.20.2523.28","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1993.1219"},{"key":"2021111418255384000_9.20.2523.29","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90034-V"},{"key":"2021111418255384000_9.20.2523.30","first-page":"424","article-title":"Segmental patterns of neuronal development in the chick hindbrain.","volume":"33","year":"1989","journal-title":"Nature"},{"key":"2021111418255384000_9.20.2523.31","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1242\/dev.113.4.1281","article-title":"Segmental origin and migration of neural crest cells in the hindbrain region of the chick embryo.","volume":"113","year":"1991","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.32","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90281-U"},{"key":"2021111418255384000_9.20.2523.33","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1242\/dev.113.2.601","article-title":"Hox-7 expression during murine craniofacial development.","volume":"113","year":"1991","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.34","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.10.1237"},{"key":"2021111418255384000_9.20.2523.35","doi-asserted-by":"publisher","DOI":"10.1038\/ng0493-299"},{"key":"2021111418255384000_9.20.2523.36","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420220306"},{"key":"2021111418255384000_9.20.2523.37","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/aja.1002020211","article-title":"Experimental analysis of Msx-1 and Msx-2 gene expression during chick mandibular morphogenesis.","volume":"202","year":"1995","journal-title":"Dev. Dynamics"},{"key":"2021111418255384000_9.20.2523.38","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(83)90318-4"},{"key":"2021111418255384000_9.20.2523.39","doi-asserted-by":"crossref","unstructured":"Noden, D.M. 1988. Interactions and fates of avian craniofacial mesenchyme. Development Suppl. 121\u2013140.","DOI":"10.1242\/dev.103.Supplement.121"},{"key":"2021111418255384000_9.20.2523.40","unstructured":"Novacek, M.J. 1993. Patterns of diversity in the mammalian skull. In The skull, Vol. 2 (ed. J.H. Hanken and B.K. Hall), pp. 438\u2013546. The University of Chicago Press, Chicago, Il."},{"key":"2021111418255384000_9.20.2523.41","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1242\/dev.117.3.961","article-title":"Xenopus Distal-less related homeo box genes are expressed in the developing forebrain and are induced by planar signals.","volume":"117","year":"1993","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.42","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90260-7"},{"key":"2021111418255384000_9.20.2523.43","doi-asserted-by":"publisher","DOI":"10.1038\/294668a0"},{"key":"2021111418255384000_9.20.2523.44","first-page":"441","article-title":"On the homology of the alisphenoid.","volume":"121","year":"1976","journal-title":"J. Anat."},{"key":"2021111418255384000_9.20.2523.45","doi-asserted-by":"publisher","DOI":"10.1038\/351748a0"},{"key":"2021111418255384000_9.20.2523.46","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90291-K"},{"key":"2021111418255384000_9.20.2523.47","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(93)90080-6"},{"key":"2021111418255384000_9.20.2523.48","unstructured":"Rieppel, O. 1993. Patterns of diversity in the reptilian skull. In The skull, Vol. 2 (ed. J. Hanken and B.K. Hall), pp. 344\u2013390. The University of Chicago Press, Chicago, Il."},{"key":"2021111418255384000_9.20.2523.49","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90620-6"},{"key":"2021111418255384000_9.20.2523.50","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(94)90060-4"},{"key":"2021111418255384000_9.20.2523.51","first-page":"1183","article-title":"Spatially restricted expression of a member of a new family of murine Distal-less homeo box genes in the developing forebrain.","volume":"3","year":"1991","journal-title":"New Biol."},{"key":"2021111418255384000_9.20.2523.52","doi-asserted-by":"crossref","unstructured":"Rubenstein, J.L.R. and L. Puelles. 1994. Homeobox gene expression during development of the vertebrate brain. In Current Topics in developmental biology, Vol. 29 (ed. R.A. Pederson), pp. 1\u201363. Academic Press, San Diego, Ca.","DOI":"10.1016\/S0070-2153(08)60546-3"},{"key":"2021111418255384000_9.20.2523.53","doi-asserted-by":"publisher","DOI":"10.1126\/science.7939711"},{"key":"2021111418255384000_9.20.2523.54","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(92)90042-I"},{"key":"2021111418255384000_9.20.2523.55","unstructured":"Sambrook, J., E.F. Fritsch, and T Maniatis. 1989. Molecular cloning, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York."},{"key":"2021111418255384000_9.20.2523.56","doi-asserted-by":"publisher","DOI":"10.1038\/ng0494-348"},{"key":"2021111418255384000_9.20.2523.57","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1242\/dev.118.3.691","article-title":"Segmental migration of the hindbrain neural crest does not arise from its segmental generation.","volume":"118","year":"1993","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.58","doi-asserted-by":"publisher","DOI":"10.1038\/358687a0"},{"key":"2021111418255384000_9.20.2523.59","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.2250"},{"key":"2021111418255384000_9.20.2523.60","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1242\/dev.113.1.239","article-title":"Segmental lineage restrictions in the chick embryo spinal cord depend on the adjacent somites.","volume":"113","year":"1991","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.61","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90646-5"},{"key":"2021111418255384000_9.20.2523.62","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90011-M"},{"key":"2021111418255384000_9.20.2523.63","first-page":"78","article-title":"Mouse n-catenin: Two isoforms, specific expression in the nervous system, and chromosomal localization of the gene.","volume":"163","year":"1994","journal-title":"Dev. Biol."},{"key":"2021111418255384000_9.20.2523.64","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1242\/dev.120.7.2065","article-title":"Multiple developmental defects in Engrailed-1 mutant mice: and early midhindbrain deletion and patterning defects in forelimbs and sternum.","volume":"120","year":"1994","journal-title":"Development"},{"key":"2021111418255384000_9.20.2523.65","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1994.1178"}],"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad.9.20.2523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T02:41:58Z","timestamp":1636944118000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad.9.20.2523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,10,15]]},"references-count":65,"journal-issue":{"issue":"20","published-print":{"date-parts":[[1995,10,15]]}},"alternative-id":["10.1101\/gad.9.20.2523"],"URL":"https:\/\/doi.org\/10.1101\/gad.9.20.2523","relation":{},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,10,15]]}}}