{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:35:49Z","timestamp":1791333349181,"version":"4.3.1"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,5,6]]},"abstract":"<jats:p>Facial recognition is central to the diagnosis of many syndromes, and craniofacial patterns may reflect common etiologies. In the pleiotropic Bardet\u2013Biedl syndrome (BBS), a primary ciliopathy with intraflagellar transport dysfunction, patients have a characteristic facial \u201cgestalt\u201d that dysmorphologists have found difficult to characterize. Here, we use dense surface modeling (DSM) to reveal that BBS patients and mouse mutants have mid-facial defects involving homologous neural crest-derived structures shared by zebrafish morphants. These defects of the craniofacial (CF) skeleton arise from aberrant cranial neural crest cell (NCC) migration. These effects are not confined to the craniofacial region, but vagal-derived NCCs fail to populate the enteric nervous system, culminating in disordered gut motility. Furthermore, morphants display hallmarks of disrupted Sonic Hedgehog (Shh) signaling from which NCCs take positional cues. We propose a model whereby Bbs proteins modulate NCC migration, contributing to craniofacial morphogenesis and development of the enteric nervous system. These migration defects also explain the association of Hirschsprung's disease (HD) with BBS. Moreover, this is a previously undescribed method of using characterization of facial dysmorphology as a basis for investigating the pathomechanism of CF development in dysmorphic syndromes.<\/jats:p>","DOI":"10.1073\/pnas.0707057105","type":"journal-article","created":{"date-parts":[[2008,4,28]],"date-time":"2008-04-28T21:26:54Z","timestamp":1209418014000},"page":"6714-6719","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":185,"title":["Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung's disease in Bardet\u2013Biedl syndrome"],"prefix":"10.1073","volume":"105","author":[{"given":"Jonathan L.","family":"Tobin","sequence":"first","affiliation":[{"name":"*Molecular Medicine Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Di Franco","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Unit, UCL Eastman Dental Institute for Oral Health Care Sciences, 256 Gray's Inn Road, London WC1X 8LD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Eichers","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"May-Simera","sequence":"additional","affiliation":[{"name":"*Molecular Medicine Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Quinlan","sequence":"additional","affiliation":[{"name":"*Molecular Medicine Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica J.","family":"Justice","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul C.","family":"Hennekam","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom; and"},{"name":"Department of Pediatrics, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Briscoe","sequence":"additional","affiliation":[{"name":"Developmental Neurobiology, National Institute for Medical Research, London NW7 1AA, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masazumi","family":"Tada","sequence":"additional","affiliation":[{"name":"**Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Mayor","sequence":"additional","affiliation":[{"name":"**Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J.","family":"Burns","sequence":"additional","affiliation":[{"name":"Neural Development Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hammond","sequence":"additional","affiliation":[{"name":"*Molecular Medicine Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom;"},{"name":"Biomedical Informatics Unit, UCL Eastman Dental Institute for Oral Health Care Sciences, 256 Gray's Inn Road, London WC1X 8LD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"Beales","sequence":"additional","affiliation":[{"name":"*Molecular Medicine Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,5,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950181206"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/498396"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116142"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-007-0435-0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02030"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1352"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01676"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1136\/jmg.36.6.437","article-title":"New criteria for improved diagnosis of Bardet-Biedl syndrome: Results of a population survey","volume":"36","author":"Beales PL","year":"1999","unstructured":"PL Beales, N Elcioglu, AS Woolf, D Parker, FA Flinter, New criteria for improved diagnosis of Bardet-Biedl syndrome: Results of a population survey. 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