p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal development
Craniofacial abnormalities are among the most prevalent congenital defects, significantly affecting appearance, function, and quality of life. While the role of genetic mutations in craniofacial malformations is recognized, the underlying molecular mechanisms remain poorly understood. In this study,...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1569533/full |
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| author | Byron Zhao Jinsook Suh Yan Zhang Eric Yin Chiho Kadota-Watanabe Chiho Kadota-Watanabe In Won Chang Jun Yaung Isabelle Lao-Ngo Nathan M. Young Reuben H. Kim Ophir D. Klein Ophir D. Klein Christine Hong |
| author_facet | Byron Zhao Jinsook Suh Yan Zhang Eric Yin Chiho Kadota-Watanabe Chiho Kadota-Watanabe In Won Chang Jun Yaung Isabelle Lao-Ngo Nathan M. Young Reuben H. Kim Ophir D. Klein Ophir D. Klein Christine Hong |
| author_sort | Byron Zhao |
| collection | DOAJ |
| description | Craniofacial abnormalities are among the most prevalent congenital defects, significantly affecting appearance, function, and quality of life. While the role of genetic mutations in craniofacial malformations is recognized, the underlying molecular mechanisms remain poorly understood. In this study, we investigate the role of p75 neurotrophin receptor (p75NTR) in craniofacial development by comparing wild-type (p75NTR+/+) mice against p75NTR-deficient (p75NTR−/−) knockout mice. We employed histology, micro-CT surface distance, volumetric analysis, and geometric morphometric analysis to assess craniofacial development and growth. On postnatal day 7 (P7), p75NTR−/− mice exhibited reduced skull length compared to wild-type controls. By P28, micro-CT analysis revealed significant reductions in calvarial bone volume and trabecular bone thickness in p75NTR−/− mice. Geometric morphometric analysis identified significant shape alterations in the nasal, parietal, and occipital regions, with p75NTR−/− mice showing a shortened cranium and tapered nasal bone morphology. These findings highlight the critical role of p75NTR in regulating postnatal craniofacial development. Disruption of p75NTR signaling impairs both the growth and morphological integrity of craniofacial structures, which may contribute to the pathogenesis of congenital craniofacial abnormalities. In the future, a better understanding of the molecular mechanisms through which p75NTR mediates craniofacial development may offer valuable insights for future targeted therapeutic strategies for craniofacial defects. |
| format | Article |
| id | doaj-art-649b70f7db494aedb9df8493b9d158e9 |
| institution | DOAJ |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-649b70f7db494aedb9df8493b9d158e92025-08-20T02:56:37ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-03-011310.3389/fcell.2025.15695331569533p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal developmentByron Zhao0Jinsook Suh1Yan Zhang2Eric Yin3Chiho Kadota-Watanabe4Chiho Kadota-Watanabe5In Won Chang6Jun Yaung7Isabelle Lao-Ngo8Nathan M. Young9Reuben H. Kim10Ophir D. Klein11Ophir D. Klein12Christine Hong13Division of Orthodontics, Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United StatesDivision of Orthodontics, Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United StatesDivision of Orthodontics, Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United StatesDivision of Orthodontics, Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United StatesDivision of Orthodontics, Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United StatesDivision of Maxillofacial and Neck Reconstruction, Department of Maxillofacial Orthognathics, Institute of Science Tokyo, Tokyo, JapanShapiro Family Laboratory of Viral Oncology and Aging Research, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United StatesShapiro Family Laboratory of Viral Oncology and Aging Research, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United StatesDivision of Orthodontics, Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA, United StatesShapiro Family Laboratory of Viral Oncology and Aging Research, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Orofacial Sciences, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Pediatrics, Cedars-Sinai Guerin Children’s, Los Angeles, CA, United StatesDivision of Orthodontics, Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United StatesCraniofacial abnormalities are among the most prevalent congenital defects, significantly affecting appearance, function, and quality of life. While the role of genetic mutations in craniofacial malformations is recognized, the underlying molecular mechanisms remain poorly understood. In this study, we investigate the role of p75 neurotrophin receptor (p75NTR) in craniofacial development by comparing wild-type (p75NTR+/+) mice against p75NTR-deficient (p75NTR−/−) knockout mice. We employed histology, micro-CT surface distance, volumetric analysis, and geometric morphometric analysis to assess craniofacial development and growth. On postnatal day 7 (P7), p75NTR−/− mice exhibited reduced skull length compared to wild-type controls. By P28, micro-CT analysis revealed significant reductions in calvarial bone volume and trabecular bone thickness in p75NTR−/− mice. Geometric morphometric analysis identified significant shape alterations in the nasal, parietal, and occipital regions, with p75NTR−/− mice showing a shortened cranium and tapered nasal bone morphology. These findings highlight the critical role of p75NTR in regulating postnatal craniofacial development. Disruption of p75NTR signaling impairs both the growth and morphological integrity of craniofacial structures, which may contribute to the pathogenesis of congenital craniofacial abnormalities. In the future, a better understanding of the molecular mechanisms through which p75NTR mediates craniofacial development may offer valuable insights for future targeted therapeutic strategies for craniofacial defects.https://www.frontiersin.org/articles/10.3389/fcell.2025.1569533/fullp75NTRCD271NGFcraniofacial developmentcraniofacial morphogenesiscalvarial development |
| spellingShingle | Byron Zhao Jinsook Suh Yan Zhang Eric Yin Chiho Kadota-Watanabe Chiho Kadota-Watanabe In Won Chang Jun Yaung Isabelle Lao-Ngo Nathan M. Young Reuben H. Kim Ophir D. Klein Ophir D. Klein Christine Hong p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal development Frontiers in Cell and Developmental Biology p75NTR CD271 NGF craniofacial development craniofacial morphogenesis calvarial development |
| title | p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal development |
| title_full | p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal development |
| title_fullStr | p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal development |
| title_full_unstemmed | p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal development |
| title_short | p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal development |
| title_sort | p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal development |
| topic | p75NTR CD271 NGF craniofacial development craniofacial morphogenesis calvarial development |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1569533/full |
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