دورية أكاديمية
Tfap2a-dependent changes in mouse facial morphology result in clefting that can be ameliorated by a reduction in Fgf8 gene dosage
| العنوان: | Tfap2a-dependent changes in mouse facial morphology result in clefting that can be ameliorated by a reduction in Fgf8 gene dosage |
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| المؤلفون: | Green, Rebecca M., Feng, Weiguo, Phang, Tzulip, Fish, Jennifer L., Li, Hong, Spritz, Richard A., Marcucio, Ralph S., Hooper, Joan, Jamniczky, Heather, Hallgrímsson, Benedikt, Williams, Trevor |
| بيانات النشر: | University of Colorado Anschutz Medical Campus. Strauss Health Sciences Library Disease Models & Mechanisms |
| سنة النشر: | 2015 |
| المجموعة: | Digital Collections of Colorado (Colorado State University) |
| مصطلحات موضوعية: | BOFS, Geometric morphometrics, Fgf signaling pathway, Craniofacial Abnormalities, Transcription Factor AP-2, Branchio-Oto-Renal Syndrome, Cleft Lip, Palate |
| جغرافية الموضوع: | Aurora (Colo.) |
| الوصف: | Includes bibliographic references. ; Failure of facial prominence fusion causes cleft lip and palate (CL/P), a common human birth defect. Several potential mechanisms can be envisioned that would result in CL/P, including failure of prominence growth and/or alignment as well as a failure of fusion of the juxtaposed epithelial seams. Here, using geometric morphometrics, we analyzed facial outgrowth and shape change over time in a novel mouse model exhibiting fully penetrant bilateral CL/P. This robust model is based upon mutations in Tfap2a, the gene encoding transcription factor AP-2α, which has been implicated in both syndromic and non-syndromic human CL/P. Our findings indicate that aberrant morphology and subsequent misalignment of the facial prominences underlies the inability of the mutant prominences to fuse. Exencephaly also occured in some of the Tfap2a mutants and we observed additional morphometric differences that indicate an influence of neural tube closure defects on facial shape. Molecular analysis of the CL/P model indicates that Fgf signaling is misregulated in the face, and that reducing Fgf8 gene dosage can attenuate the clefting pathology by generating compensatory changes. Furthermore, mutations in either Tfap2a or Fgf8 increase variance in facial shape, but the combination of these mutations restores variance to normal levels. The alterations in variance provide a potential mechanistic link between clefting and the evolution and diversity of facial morphology. Overall, our findings suggest that CL/P can result from small gene-expression changes that alter the shape of the facial prominences and uncouple their coordinated morphogenesis, which is necessary for normal fusion. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Print #M121. Tfap2a-dependent changes in mouse facial morphology result in clefting that can be ameliorated by a reduction in Fgf8 gene dosage. 2015; Health Sciences Library Photograph Collection and Special Collections, University of Colorado Anschutz Medical Campus; Publications.; Green, Rebecca M., Feng, Weiguo, Phang, Tzulip, Fish, Jennifer L., Li, Hong, Spritz, Richard A., Marcucio, Ralph S., Hooper, Joan, Jamniczky, Heather, Hallgrimsson, Benedikt, Williams, Trevor, Tfap2a-dependent changes in mouse facial morphology result in clefting that can be ameliorated by a reduction in Fgf8 gene dosage. Disease Models & Mechanisms (2015)7. doi:10.1242/dmm.017616; http://hdl.handle.net/10968/1158Test; http://dx.doi.org/doi:10.1242/dmm.017616Test |
| DOI: | 10.1242/dmm.017616 |
| الإتاحة: | https://doi.org/10.1242/dmm.017616Test http://hdl.handle.net/10968/1158Test |
| حقوق: | Copyright of the original work is retained by the author(s). This article was created with the support of the Open Access Fund Program, formerly available through the Strauss Health Sciences Library, an initiative that helped to finance the author processing fees of OA journals. ; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0Test/), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| رقم الانضمام: | edsbas.5F3CF76E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1242/dmm.017616 |
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