Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung's disease in Bardet-Biedl syndrome
| العنوان: | Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung's disease in Bardet-Biedl syndrome |
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| المؤلفون: | Monica J. Justice, Masazumi Tada, Roberto Mayor, Monica D. Garcia, Peter Hammond, James R. Lupski, Erica R. Eichers, Raoul C.M. Hennekam, James Briscoe, Jonathan L. Tobin, Matt Di Franco, Helen May-Simera, Alan J. Burns, Robyn J. Quinlan, Philip L. Beales, Jiong Yan |
| المساهمون: | ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Paediatric Genetics |
| المصدر: | Proceedings of the National Academy of Sciences; Vol 105 Proceedings of the National Academy of Sciences of the United States of America, 105(18), 6714-6719. National Academy of Sciences |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | congenital, hereditary, and neonatal diseases and abnormalities, Enteric Nervous System, Craniofacial Abnormalities, 03 medical and health sciences, Mice, 0302 clinical medicine, Cranial neural crest, Imaging, Three-Dimensional, Bardet–Biedl syndrome, Intraflagellar transport, Cell Movement, medicine, Animals, Humans, Hedgehog Proteins, Cilia, Hirschsprung Disease, Craniofacial, Sonic hedgehog, Hirschsprung's disease, Bardet-Biedl Syndrome, Zebrafish, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, Neural crest, Anatomy, Biological Sciences, Zebrafish Proteins, medicine.disease, Wnt Proteins, Ciliopathy, Phenotype, Neural Crest, Mutation, biology.protein, NIH 3T3 Cells, Gastrointestinal Motility, Neuroscience, 030217 neurology & neurosurgery, Signal Transduction |
| الوصف: | Facial recognition is central to the diagnosis of many syndromes, and craniofacial patterns may reflect common etiologies. In the pleiotropic Bardet–Biedl syndrome (BBS), a primary ciliopathy with intraflagellar transport dysfunction, patients have a characteristic facial “gestalt” 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. |
| اللغة: | English |
| تدمد: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0707057105 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a3166b4274d44c4ee46ac9ab30765089 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a3166b4274d44c4ee46ac9ab30765089 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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| DOI: | 10.1073/pnas.0707057105 |